Rena R. Wing - US grants

The long-term objective of the project continues to be the development of a behavioral weight control program for obese patients with Type II diabetes. The proposed study is designed to investigate the effect of exercise, as an adjunct to caloric restriction, in the treatment of Type II diabetes, and, specifically, to determine whether there are dose-response relationships between the amount of exercise expenditure included in the program and changes in body weight or metabolic control. The effect of involving the spouse in the treatment program on long-term adherence to diet and exercise will also be assessed. One hundred fifty obese patients with Type II diabetes will be randomly assigned to behavioral weight control programs varying in the amount of caloric expenditure from structured exercise (O, 450, or 900 calories/week) and in the amount of spouse support (spouse included in assessments and treatment or spouse included in assessments only). Fitness, eating habits, serum lipids, blood pressure, and blood sugar control will be measured at pretreatment, the end of the 15-week program, and at 1-year follow-up. The proposed project will also analyze individual differences which may affect weight loss and/or the metabolic response to weight loss and will study the relationship between spouse pairs in pretreatment eating and exercise behaviors, and in the magnitude of habit change during treatment.

The overall goal will be the development of a dietary intervention method that is capable of producing large sustained weight losses and is thus suitable for use in clinical trials related to obesity. A recent study by the investigators showed that a method based on principles of antecedent control, namely the provision of food to participants, was successful in almost doubling weight losses over a 12 month period compared to those attained in a standard behavioral weight control program. These weight losses were associated with substantial improvements in cardiovascular risk factors. The purpose of the present proposal is to better understand the factors responsible for the positive effects of this intervention and to extend the principles of antecedent control to the area of maintenance. Study 1 will determine whether there are long-term benefits to food provision by reexamining the 202 participants in the original study one year after the end of treatment. Study 2 will investigate the factors related to the successful food provision intervention by comparing the additive effects of standard behavioral treatment and the three central components of food provision: structured meal plans, prepackaged food and subsidy of the food. It will also explore theoretical mechanisms which may underlie the food provision effect, specifically decision making and stimulus control. Study 3 will evaluate the effectiveness of extend the food provision methodology to families. Overweight spouse pairs will be randomized to treatments in which either one member of the pair participates in treatment and receives food, or both members of the pair participate and are provided with food. Study 4 will determine whether the principles of antecedent control can also be applied to exercise. Participants will be randomized to weight control programs which include either the usual exercise instructions or structured plans for exercise and free passes to exercise facilities near their home. It is hypothesized that providing food for the obese spouse as well as the patient, and providing antecedent control for exercise through structured plans and free passes will both improve the maintenance of weight loss. The proposed studies will provide important data on the effect of these interventions on eating behavior, activity, and body weight, and hopefully result in a more successful long-term weight loss intervention.

Binge eating is a prevalent problem among obese individuals. Obese binge eaters meet DSM-III criteria for bulimia and report disturbed eating behaviors, maladaptive cognitions about diet and weight, and marked dysphoria. To date these patients have been treated primarily in weight control programs, but unfortunately these programs fail to modify binge behaviors or to produce long-term changes in weight. The proposed project represents one of the first efforts to develop a treatment program specifically for obese binge eaters. The goals of this treatment program are to ameliorate the eating disorder and reduce body weight. The specific aim of the project is to test the effectiveness of a cognitive behavioral treatment that has been used successfully with normal weight bulimia nervosa patients in the treatment of obese binge eaters. One hundred and eight obese women who meet DSM-III-R criteria for bulimia will be randomly assigned to either cognitive behavioral treatment for bulimia (BULIMIA), behavioral weight control (WEIGHT) or a delayed treatment control. The treatment programs will consist of 22 individual therapy sessions over a 6 month period followed by 6 maintenance sessions. Patients in the three conditions will be interviewed before and after the 6 month treatment interval to assess changes in binge behaviors, weight, cognitions about weight and shape, and mood. The delayed treatment condition will then receive the program that appears most effective. Patients in the other conditions will be reassessed after 6 and 12 months to compare the long-term effectiveness of the progams. This project will provide information about the course of bulimia in obese women, the short- and long-term effects of two different treatments on the behavioral, cognitive, and affective components of bulimia, and the role of binge eating in the maintenance of obesity.

This is a competitive renewal of the University of Pittsburgh Obesity/Nutrition Research Center (ONRC). The goal of this ONRC is to develop more effective interventions for the prevention and treatment of obesity. This focus is significant since there are 50 million Americans who are obese, and current efforts at treatment are only moderately successful. The University of Pittsburgh is uniquely qualified to focus on intervention research, since the Director, Dr. Rena R. Wing, is internationally known for her research on this topic. The Associate Director, Dr. David Kelley brings complementary expertise in the area of metabolism. The University of Pittsburgh currently has over 60-funded research projects related to obesity and nutrition. These projects are being executed by researchers in the Departments of Psychiatry, Epidemiology, Medicine, Pediatrics, Obstetrics and Gynecology, and Psychology. The goal of the ONRC is to promote multidisciplinary research between these investigators and to encourage young investigators to enter the field. Evidence that the ONRC is achieving these goals comes from new funding received as the Lifestyle Resource Core of the DPP, as one of two centers in the Health, Aging, and Body Composition Study, and the reorientation of a program project on preeclampsia to focus on lipids and obesity; in addition 9 out of 15 pilot feasibility grants funded before 5/96 have led to additional funding for obesity research. The goals of the ONRC are achieved through a speaker series, a pilot feasibility grant program, and five Core Facilities: An Administrative Core (with a statistical subcore), a Metabolic Body Composition, and Clinical Assessment Core, a Biochemistry and Genetics Core, a Behavior Core, and an Intervention Core. Each of these cores is designed to increase collaborative research and bring new investigators into the field through provision of shared resources and staff; consulting assistance; development of new methods; and providing training opportunities. The focus of the Pittsburgh ONRC on intervention research should complement that of other centers and promote scientific research on the critical issues of treatment and prevention.

Diabetes mellitus is a major cause of morbidity and mortality in the United States, and individuals with impaired glucose tolerance (IGT) or a history of gestational diabetes (GDM) are at increased risk of developing this disease. Research to test whether it is possible to prevent the occurrence of NIDDM is a national priority. The University of Pittsburgh proposes a primary prevention trial that optimally tests the hypothesis that NIDDM is preventable through weight loss and physical activity and simultaneously addresses whether an intervention that is more easily adopted by the health care system is of benefit. Targeted advertisement and chart review will be used to identify 100 subjects with IGT (confirmed on repeat OGTT and with at least one 2-hour BS>170); 100 GDM subjects will be identified from a registry of over 1000 women with GDM; we aim for 40% of participants to be African American. These 200 high risk subjects will be randomized to a control group, a standard life-style intervention (SLI), or an enhanced life-style intervention (ELSI). The goals for the two intervention groups will be a 10% weight loss and 3 hours/week of physical activity. To achieve these goals, the SLI group will participate in a standard diet/exercise program that could be easily implemented by the health system; community-led exercise groups will also be available. The ELSI group will be given enhanced treatment to optimally test the prevention hypothesis; these subjects will be seen individually on a monthly basis; intervention will be prescribed as needed to achieve and maintain the weight and exercise goal. The primary outcome will be development of NIDDM (WHO criteria; confirmed by second test). Other endpoints will be changes in glucose, insulin resistance, insulin secretion, and the cardiovascular risk profile. During screening, some subjects will be identified as having non-fasting diabetes (NFD; FBS <140; 2 hour BS>200). These subjects will participate in a secondary prevention trial using a 2 x 2 factorial design with the two life-style conditions (SLI vs ESLI) crossed with 2 drug conditions (metformin vs placebo). The primary outcome measures for this secondary prevention study will be development of fasting hyperglycemia and incidence or progression of diabetic complications. The University of Pittsburgh is well qualified to participate in this trial as we have extensive experience in life-style interventions, exercise, clinical trials, diabetic complications, and in the medical management of diabetes.

The long-term objective of the project continues to be the development of an effective behavioral weight control program for obese patients with type II diabetes. A second goal, added in the current submission, is to determine whether behavioral techniques can also be successfully applied in those at risk for type II diabetes, namely obese individuals with a family history of diabetes. The proposed project is designed to investigate the effects of a structured exercise program and a structured very low calorie diet, used singly or in combination, within the context of a long-term behavioral treatment program. Previous studies evaluating diet and exercise interventions have had small sample size, included only short periods of structured exercise (thus potentially underestimating the effectiveness of exercise) and focused entirely on calorie restriction (rather than also attempting to modify the fat content of the diet). The current study will improve the methodology and the treatment interventions and will determine which type of intervention is most effective in producing weight loss, improving glycemic control, and reducing coronary heart disease risk factors in those with diabetes and in those at risk for the disease. We propose to recruit 200 obese type II diabetic patients and 200 obese subjects who have a family history of diabetes. These subjects will be randomly assigned to Usual Care, or to Behavioral Weight Control Programs focusing on Diet Only, Exercise Only, or the Combination. All treatments win be conducted over a 2 year. period with intervention meetings held over this entire period. Weight, glucose and insulin responses to an oral glucose load, HbA1, lipids, blood pressure, fitness, and eating and exercise habits will be assessed at baseline, 1 year and 2 years. This study will provide important information on whether diet, exercise, or the combination is the most effective intervention for type 11 diabetic patients and those who are obese and have a family history of the disease. In addition, treating diabetic individuals and those at risk within the same study will allow us to determine whether these two groups differ in adherence to the programs and/or in their physiological responses to treatment, and whether the same intervention is most effective for both groups.

Diabetes mellitus is a major cause of morbidity and mortality in the United States, and individuals with impaired glucose tolerance (IGT) or a history of gestational diabetes (GDM) are at increased risk of developing this disease. Research to test whether it is possible to prevent the occurrence of NIDDM is a national priority. The University of Pittsburgh proposes a primary prevention trial that optimally tests the hypothesis that NIDDM is preventable through weight loss and physical activity and simultaneously addresses whether an intervention that is more easily adopted by the health care system is of benefit. Targeted advertisement and chart review will be used to identify 100 subjects with IGT (confirmed on repeat OGTT and with at least one 2-hour BS>170); 100 GDM subjects will be identified from a registry of over 1000 women with GDM; we aim for 40% of participants to be African American. These 200 high risk subjects will be randomized to a control group, a standard life-style intervention (SLI), or an enhanced life-style intervention (ELSI). The goals for the two intervention groups will be a 10% weight loss and 3 hours/week of physical activity. To achieve these goals, the SLI group will participate in a standard diet/exercise program that could be easily implemented by the health system; community-led exercise groups will also be available. The ELSI group will be given enhanced treatment to optimally test the prevention hypothesis; these subjects will be seen individually on a monthly basis; intervention will be prescribed as needed to achieve and maintain the weight and exercise goal. The primary outcome will be development of NIDDM (WHO criteria; confirmed by second test). Other endpoints will be changes in glucose, insulin resistance, insulin secretion, and the cardiovascular risk profile. During screening, some subjects will be identified as having non-fasting diabetes (NFD; FBS <140; 2 hour BS>200). These subjects will participate in a secondary prevention trial using a 2 x 2 factorial design with the two life-style conditions (SLI vs ESLI) crossed with 2 drug conditions (metformin vs placebo). The primary outcome measures for this secondary prevention study will be development of fasting hyperglycemia and incidence or progression of diabetic complications. The University of Pittsburgh is well qualified to participate in this trial as we have extensive experience in life-style interventions, exercise, clinical trials, diabetic complications, and in the medical management of diabetes.

weight loss; cognitive behavior therapy; behavior modification; exercise; biomedical facility; diet therapy; nutrition disorder chemotherapy; reducing diet; weight control; behavioral /social science research tag; clinical research; human subject; nutrition related tag;

weight loss; information dissemination; weight control; health education; obesity; teacher; curriculum; behavioral /social science research tag;

(Revised Abstract) Overweight and obesity are major health problems in the United States, affecting more than 50% of adults. The long-term consequences of being overweight or obese include increased mortality and increased morbidity from a variety of associated disease states. Short-term weight loss has been demonstrated to ameliorate obesity-related metabolic abnormalities and cardiovascular disease risk factors. However, observational studies have raised concerns about negative effects of weight loss and weight cycling over the long term, including increased mortality. Look AHEAD (Action For Health in Diabetes) is a 2-armed randomized controlled clinical trial studying overweight and obese volunteers with type 2 diabetes at 16 clinical centers. Approximately 5,000 volunteers with type 2 diabetes aged 45-75 years with body mass index > 25 kg/m will be recruited, including approximately equal numbers of men and women and at least 33% participants from ethnic minority groups. The primary objective of Look AHEAD is to examine the long-term health effects of an intensive Lifestyle Intervention designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity. The Lifestyle intervention is implemented with individual supervision and group sessions and aims to achieve at least a 7% decrease in weight from baseline and 175 minutes per week in physical activity on average and to sustain these goals. This program will be compared to a control condition involving a program of Diabetes Support and Education. The primary hypothesis is that the incidence rate of the first post-randomization occurrence of a composite outcome, which includes cardiovascular death (including fatal myocardial infarction and stroke), non-fatal myocardial infarction, and non-fatal stroke, over a planned follow-up period of up to 11.5 years will be reduced among participants assigned to the Lifestyle Intervention compared to those assigned to Diabetes Support and Education. The study is projected to have 90% probability of detecting an 18% difference in this primary outcome between the 2 groups. A composite secondary outcome of all deaths, CVD events, and CVD procedures has been defined. Additional outcomes include: diabetes control and complications, fitness, general health, health-related quality of life, and psychological outcomes. The cost and cost effectiveness of the Lifestyle Intervention relative to Diabetes Support and Education will be assessed.

Over half of US adults are overweight. Treatments are currently available to help these individuals lose wright, but most will regain their loss. Thus, a major problem in the treatment of obesity is prevention of weight regain. An innovative new approach that we believe may be particularly effective in preventing weight regain is the use of an interactive computerized intervention. We propose to use the Internet and e-mail to deliver an intervention that specifically focuses on a weight gain prevention and provides all of the basic components of a cognitive behavioral approach, including goal setting, self-monitoring, feedback, prompting, problem solving motivation enhancement reinforcement and social support. We believe that Internet interventions may be particularly useful for maintenance because frequent contact can be continued long-term with low cost and maximal flexibility; the anonymity may reduce embarrassment about weight gain; educational information can be provided when it is relevant to the participant; all aspects of the intervention can be individualized and tailored to the participant; data can be easily transmitted and analyzed for trends; immediate feedback can be provided to reinforces successful achievement and catch problems early; and participants can provide ongoing social support to each other. We will test this interactive computerized intervention (ICI) by recruiting 160 individuals who lost at least 10 percent of their weight in the past year. Prior studies suggest that individuals who lost weight just 1 year ago are at greatest risk of weight regain. We will purposely recruit individuals who have lost weight using various different approaches. These individuals will be randomly assigned to a no-treatment control condition or to use the ICI program for 18 months. Outcomes will be assessed at 6, 12, and 18 months. The primary outcomes will be weight change from 0 to 18 months and the proportion who regain less than 2.5 kg over 18 months. Adherence to the intervention and acceptability of the various components will be analyzed to determine the feasibility of delivering maintenance interventions via computer. The proposed ICI intervention is innovative because it explicitly focuses on prevention of weight regain; it is developed for individuals who have lost weight in a variety of ways and need help with maintenance of weight loss; it makes use of Internet and e-mail technology that has not previously been applied to the area of the weight control (and certainly not to maintenance); and uses computer technology creatively to maximize the delivery of all of the basic components of a cognitive behavioral intervention for weight loss maintenance.

(Revised Abstract) Overweight and obesity are major health problems in the United States, affecting more than 50% of adults. The long-term consequences of being overweight or obese include increased mortality and increased morbidity from a variety of associated disease states. Short-term weight loss has been demonstrated to ameliorate obesity-related metabolic abnormalities and cardiovascular disease risk factors. However, observational studies have raised concerns about negative effects of weight loss and weight cycling over the long term, including increased mortality. Look AHEAD (Action For Health in Diabetes) is a 2-armed randomized controlled clinical trial studying overweight and obese volunteers with type 2 diabetes at 16 clinical centers. Approximately 5,000 volunteers with type 2 diabetes aged 45-75 years with body mass index > 25 kg/m will be recruited, including approximately equal numbers of men and women and at least 33% participants from ethnic minority groups. The primary objective of Look AHEAD is to examine the long-term health effects of an intensive Lifestyle Intervention designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity. The Lifestyle intervention is implemented with individual supervision and group sessions and aims to achieve at least a 7% decrease in weight from baseline and 175 minutes per week in physical activity on average and to sustain these goals. This program will be compared to a control condition involving a program of Diabetes Support and Education. The primary hypothesis is that the incidence rate of the first post-randomization occurrence of a composite outcome, which includes cardiovascular death (including fatal myocardial infarction and stroke), non-fatal myocardial infarction, and non-fatal stroke, over a planned follow-up period of up to 11.5 years will be reduced among participants assigned to the Lifestyle Intervention compared to those assigned to Diabetes Support and Education. The study is projected to have 90% probability of detecting an 18% difference in this primary outcome between the 2 groups. A composite secondary outcome of all deaths, CVD events, and CVD procedures has been defined. Additional outcomes include: diabetes control and complications, fitness, general health, health-related quality of life, and psychological outcomes. The cost and cost effectiveness of the Lifestyle Intervention relative to Diabetes Support and Education will be assessed.

weight loss; urinary incontinence; weight control; human therapy evaluation; cooperative study; clinical trials; clinical research; human subject;

DESCRIPTION (provided by applicant): A commonly held (although controversial) belief is "once an alcoholic, always an alcoholic". However, in the area of weight control, people appear to have the opposite impression - that successfully reduced obese individuals should be able to maintain their weight loss "by eating and exercising like normal [weight] individuals". The proposed research will determine whether successfully reduced obese individuals are able to maintain a normal body weight using behaviors similar to normal weight individuals or whether the reduced obese must work harder to maintain their body weight. This comparison is of interest since both groups have apparently managed to control their body weight despite living in an obesogenic environment. The proposed study compares successful long-term weight loss maintainers (n=200), defined as individuals who have reduced from overweight/obese to normal weight and maintained the weight loss for a minimum of 5 years, with normal weight controls (n=200) with no history of obesity. The groups will be compared on their eating and exercise behaviors using tritrac accelerometers and 24-hour recalls to provide a more detailed assessment than used in previous studies of successful weight loss maintainers. We will then compare the two groups on the extent to which they have modified their environment to support these behaviors, their preferences for these behaviors, their motivation for maintaining these behaviors, and their quality of life. Findings from this study will have important implications for understanding whether successful weight loss maintainers can at some point regulate their weight in ways similar to normal weight controls or whether they must always work harder to accomplish this. Such information is important for providing an accurate picture to those individuals seeking to lose weight of what it takes to be a successful weight loss maintainer.

DESCRIPTION (provided by applicant): A commonly held (although controversial) belief is "once an alcoholic, always an alcoholic". However, in the area of weight control, people appear to have the opposite impression - that successfully reduced obese individuals should be able to maintain their weight loss "by eating and exercising like normal [weight] individuals". The proposed research will determine whether successfully reduced obese individuals are able to maintain a normal body weight using behaviors similar to normal weight individuals or whether the reduced obese must work harder to maintain their body weight. This comparison is of interest since both groups have apparently managed to control their body weight despite living in an obesogenic environment. The proposed study compares successful long-term weight loss maintainers (n=200), defined as individuals who have reduced from overweight/obese to normal weight and maintained the weight loss for a minimum of 5 years, with normal weight controls (n=200) with no history of obesity. The groups will be compared on their eating and exercise behaviors using tritrac accelerometers and 24-hour recalls to provide a more detailed assessment than used in previous studies of successful weight loss maintainers. We will then compare the two groups on the extent to which they have modified their environment to support these behaviors, their preferences for these behaviors, their motivation for maintaining these behaviors, and their quality of life. Findings from this study will have important implications for understanding whether successful weight loss maintainers can at some point regulate their weight in ways similar to normal weight controls or whether they must always work harder to accomplish this. Such information is important for providing an accurate picture to those individuals seeking to lose weight of what it takes to be a successful weight loss maintainer.

[unreadable] DESCRIPTION (provided by applicant): Look AHEAD is randomized clinical trial examining the long-term health effects of an intensive weight loss intervention in approximately 5,145 overweight volunteers with type 2 diabetes. Participants are randomized to an intensive lifestyle intervention designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity, or to a control program of diabetes support and education. The primary outcome of Look AHEAD is the aggregate occurrence of severe cardiovascular events (fatal and non-fatal Ml and stroke and cardiovascular deaths) over a planed follow-up of 11.5 years. The original grant application provided funding for the first 7 years of the study (1 year for study design and 6 for execution of the trial). The present grant application is for an additional 7 years of funding to complete the Look AHEAD trial. All aspects of the study have proceeded extremely well - the sample of 5,145 was recruited on time; retention has been excellent and the intervention has been effective in producing initial weight loss and maintaining it over time. All 16 clinical sites have been successful in recruitment, retention, and delivery of the intervention and the DSMB has been very positive about the execution of the trial. The present application reviews the overall design of Look AHEAD, progress to date, and plans for the future. Specific Aims are to retain the cohort over time, continue to complete annual in-person visits and semi-annual telephone interviews for outcome assessments and continue to administer the lifestyle intervention. These procedures will enable us to analyze the effects of the intervention on serious cardiovascular- related factors and complications, and cost-effectiveness of the intervention. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] The primary goal of this program is to train post-doctoral fellows to conduct research related to changing behavior to reduce the burden of cardiovascular disease (CVD). The Brown University Centers for Behavioral and Preventive Medicine (CBPM) provides a wealth of research training experiences to address the most prominent lifestyle risk factors for CVD, cigarette smoking, adverse diet, obesity, and physical inactivity. Specifically, there are opportunities to learn to use multidisciplinary approaches to treat healthy and medically ill populations (e.g. individuals with diabetes; participants in cardiovascular rehabilitation programs), deliver services in unique settings (e.g., emergency departments, neonatal intensive care units, after cardiovascular procedures), and use innovative channels of delivery (Internet, telephone, print) to more efficiently disseminate interventions. There are on-going collaborations between behavioral researchers at the CBPM and faculty in the Brown Department of Medicine and Department of Community Health. Currently funded clinical trials evaluate the effect of behavior change on cardiovascular endpoints, studies of genetic and environmental contributions to health behaviors and CVD, and projects assessing the role of psychosocial factors in cardiovascular disease and adherence to behavior change recommendations. The strength and competitiveness of the research and training programs in the CBPM attract outstanding candidates for research fellowships. Program faculty have an outstanding history of successful mentoring. Our aim will be to recruit three fellows each year, with two M.D. fellows recruited over the project. Training will be highly individualized with all fellows developing excellent core competencies in areas such as CVD epidemiology, clinical trials related to behavioral risk factors; and research skills. Fellows will also develop a complementary set of specialized competencies specific to their area of research (i.e., tobacco use, obesity, or physical activity). A formal curriculum includes both formal didactics (i.e., coursework and seminars) and mentored research experiences. The mentoring team will be headed by a senior behavioral scientist; with a physician or population scientist and a junior faculty member as secondary mentors. An individual training plan, constructed with the fellow's unique training needs in mind, will outline the competencies, mentoring arrangement, training activities, and objectives for each fellow. Formal mechanisms will be in place to monitor and evaluate each fellow's progress toward developing competencies. We believe the strengths of our faculty, funded research opportunities, and training record make us uniquely qualified to offer this training program in behavior change and CVD. (End of Abstract) [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Look AHEAD is randomized clinical trial examining the long-term health effects of an intensive weight loss intervention in approximately 5,145 overweight volunteers with type 2 diabetes. Participants are randomized to an intensive lifestyle intervention designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity, or to a control program of diabetes support and education. The primary outcome of Look AHEAD is the aggregate occurrence of severe cardiovascular events (fatal and non-fatal Ml and stroke and cardiovascular deaths) over a planed follow-up of 11.5 years. The original grant application provided funding for the first 7 years of the study (1 year for study design and 6 for execution of the trial). The present grant application is for an additional 7 years of funding to complete the Look AHEAD trial. All aspects of the study have proceeded extremely well - the sample of 5,145 was recruited on time;retention has been excellent and the intervention has been effective in producing initial weight loss and maintaining it over time. All 16 clinical sites have been successful in recruitment, retention, and delivery of the intervention and the DSMB has been very positive about the execution of the trial. The present application reviews the overall design of Look AHEAD, progress to date, and plans for the future. Specific Aims are to retain the cohort over time, continue to complete annual in-person visits and semi-annual telephone interviews for outcome assessments and continue to administer the lifestyle intervention. These procedures will enable us to analyze the effects of the intervention on serious cardiovascular- related factors and complications, and cost-effectiveness of the intervention.

[unreadable] DESCRIPTION (provided by applicant): Obesity has reached epidemic proportions and represents a serious public health problem in the United States. Efforts to treat obesity have been only moderately successful, and attention has shifted toward prevention of weight gain, rather than treatment of obesity. Although average weight gain from pre- pregnancy to one-year postpartum is 2 kg, approximately 25 percent of women gain 5 kg or more during this period. Moreover, a recent study found that nearly 44 percent of normal weight women who had retained significant amounts of weight (M= 4.8 kg) at 12 months postpartum became overweight later in life. Thus, the period surrounding pregnancy appears to be an important time for prevention efforts. The single strongest predictor of weight gain from pre-to post-pregnancy is the magnitude of weight gained during pregnancy. The Institute of Medicine (IOM) has formulated specific recommendations for healthy weight gain during pregnancy. However, more than one-third of normal weight women and two thirds of overweight women exceed recommended levels of weight gain during pregnancy. Thus, helping women gain the recommended amount during pregnancy through healthy eating and physical activity would make a major contribution to preventing excessive weight retention. The principal aim of this study is to determine whether behavioral lifestyle intervention during pregnancy can reduce the number of normal weight and overweight women who exceed the IOM recommendations for weight gain during pregnancy. We propose to recruit 400 primiparous women and randomly assign these women to receive usual care or Intervention to Promote Healthy Weight Gain During Pregnancy. The Intervention group will receive weekly educational materials, weight monitoring with feedback, and supportive phone calls. All women will be followed from early pregnancy to 1-year postpartum. We believe this project is significant because it deals with the prevention of weight gain, which is a major health problem. The study is also innovative; there have been no adequately powered randomized controlled trials evaluating the effects of a behavioral lifestyle intervention delivered during pregnancy to promote healthy weight gain and prevent sustained postpartum weight retention. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06)-Enabling Technologies and Specific Challenge Topic 06-OD(OBSSR)-101* Using new technologies to improve or measure adherence. Overweight/obesity is a major health problem that affects over two-thirds of Americans, increases morbidity and mortality and has annual medical costs exceeding $75 billion. Although many Americans indicate that they are trying to lose weight, adherence to weight loss regimens is often poor. Programs are needed that can improve adherence and weight loss for overweight/obese individuals. Physicians play an important role in motivating patients to improve health behaviors and recent reviews suggest that having physicians advise patients to lose weight and then referring patients to an effective program produces the best behavior change and maintenance. The problem, however, is that physicians currently have limited options for such referrals. The challenge for the field is to develop a program to which physicians can refer their overweight/obese patients. The program must be low cost, easily accessible, and must promote adherence to the weight loss regimen and consequently improve weight loss outcomes. The goal of this Challenge Grant application is to develop and test an innovative web-based program that would provide an accessible and effective approach to enhancing adherence to clinical recommendations for weight loss. If effective, the program would provide an outstanding resource for physicians and their patients and could consequently have important clinical and public health impact. We propose to develop a program based on our prior research that uses innovative Internet technology to provide a low cost, easily disseminated program that captures two critical elements of effective behavioral weight loss programs-namely, training in key behavioral weight control strategies and increased participant accountability. Patients, referred by their physician for weight loss, will be offered a 12 week program that they can view at their convenience on their computer. The program will use Web-based interactive multi-media approaches for presentation of the behavioral skills and provide a Web-based form for submission of self- monitoring and weight data;to maximize patient accountability, the program will include a system of automated feedback for participants, which comments on their weight loss to date and their performance within several behavioral weight-loss domains, with suggestions tailored to the characteristics and performance of the individual. Periodic reports on the patients'progress will also be sent to the referring physician. We will test this program in a randomized trial with 250 patients referred by their physicians who will be randomly assigned to either Internet Education (Control) (N=125) or to the Innovative Technology program (N=125). Participants in both groups will receive a 12 week Internet program of either basic weight loss education or the Innovative Technology program and will be weighed at the start and end of the 3 month program and at 3 month follow- up. The primary hypothesis is that patients who are assigned to the Innovative Technology program will achieve larger average weight losses than those in the control group over the 12-week program. Secondary hypotheses are that the Innovative technology group will adhere better over the 12-weeks (assessed by log-ins to the web site and self-reported changes in diet and activity) and achieve better weight losses at 6 months than the control group. The proposed project addresses the significant problem of obesity and uses innovative technology to improve adherence to a behavioral weight loss strategies. If the program is effective, it would provide an outstanding resource for physicians to use with their patients and thus would have tremendous clinical impact. The proposed project addresses the significant problem of obesity and uses innovative technology to improve adherence to a behavioral weight loss strategies. If the program is effective, it would provide an outstanding resource for physicians to use with their patients and thus would have tremendous clinical impact.

DESCRIPTION (provided by applicant): Young adults, age 20-35, experience the greatest rate of weight gain, averaging 1 to 2 pounds per year. This weight gain is associated with a worsening in cardiovascular risk factors and an increase in the prevalence of metabolic syndrome. Given the difficulties in producing sustained weight loss later in life, preventing weight gain from occurring during young adulthood is critical to curbing the obesity epidemic. This project involves two linked R01 applications--a Clinical Coordinating Center application submitted by Dr. Rena Wing, The Miriam Hospital, and a Data Coordinating Center, submitted by Dr. Mark Espeland, Wake Forest University School of Medicine. The purpose of the project is to test two interventions to prevent weight gain in young adults. Both interventions are based on a self-regulation approach that we have shown can help prevent weight regain in recent weight losers. Key aspects of this self-regulation include daily self-weighing, use of the information from the scale to know when adjustments in eating and activity are needed, behavioral skills to modify these behaviors, and small reinforcements for successful prevention of weight gain. One self-regulation intervention is focused on making small consistent changes in eating and exercise behavior to prevent weight gain;the other emphasizes periodic larger changes in eating and exercise behavior that result in small weight losses. These interventions will be compared to each other and to a control condition in a 3-armed randomized controlled clinical trial. The study will involve 600 adults (300 at the Miriam Hospital clinical site and 300 at the University of North Carolina clinical site), aged 18-35 with a BMI of 23-30, who are randomly assigned to 1) control;2) self-regulation intervention with small behavior changes or 3) self-regulation with large behavior changes. Participants will be recruited over 18 months and will be followed from randomization until the end of the grant, resulting in 24-48 months of follow-up (mean=3 years). The primary hypothesis is that the magnitude of weight gain across an average planned follow-up of 3 years will differ among the three groups (a priori hypothesis is that weight gain will be greatest in control, intermediate in small changes, and least in the large change condition). Secondary hypotheses will compare the three groups on the proportion gaining weight (defined as >1lb over baseline), changes in cardiovascular risk factors, and changes in the process measures (such as diet, physical activity, and dietary restraint). This project focuses on weight gain in young adults-a critical time for the prevention of obesity-and tests innovative approaches based on self-regulation of body eight. This approach shows promise for reducing weight gain and thereby improving long-term cardiovascular health. (End of Abstract)

DESCRIPTION (provided by applicant): This application is for an NIDDK Multi-Center Clinical Study Implementation Planning Grant (U34) to plan a clinical trial on the efficacy of lifestyle intervention to treat obese men with erectile dysfunction (ED). We have identified the 2 clinical centers and coordinating center and a team of well-established experts in ED, lifestyle intervention, recruitment and retention of large cohorts and coordinating multi-center trials. The U-34 planning phase will allow us to complete the scientific planning and administrative activities that are required to prepare to recruit subjects for this trial. ED, defined as the consistent inability to achieve and/or maintain an erection sufficient for sexual performance, is a significant public health concern because of its prevalence among middle aged men, its strong association with diminished quality of life, and its recently-established link to endothelial dysfunction and likely role as a harbinger of cardiovascular disease (CVD). Recent studies suggest that that lifestyle intervention (weight loss and increased activity) may offer a promising new approach that could improve ED as well as reducing CVD risk. A definitive randomized trial is needed to determine whether lifestyle intervention is effective for ED and to identify those men who are most likely to respond to lifestyle change. We propose a multi-center randomized controlled trial evaluating lifestyle intervention (weight loss and physical activity) to treat obese men with ED. This project, entitled Lifestyle Intervention to Treat Erectile Function (LITE), will include 300 obese men with ED from two clinical centers who will be randomly assigned to an intensive lifestyle intervention (based on protocols used successfully in several recent NIDDK trials) or delayed treatment control and followed at 6 and 12 months post-randomization. The primary goal is to determine whether randomization to an intensive lifestyle intervention results in greater improvement in ED compared to the control condition. We will also compare the lifestyle intervention and control conditions on normalization of ED, cardio-metabolic risk factors, lower urinary tract symptoms (LUTS), and patient well-being at 12-months and identify baseline characteristics that moderate the effect of treatment, potentially identifying men most likely to experience improved or normalized erectile function. Blood samples will be collected to assess biomarkers of oxidative damage, endothelial function and inflammation to investigate the mechanisms by which lifestyle intervention improves ED . Since ED may be a harbinger of CVD, lifestyle interventions may be of particular importance because they may not only be used as a first-line treatment for ED, but also may prevent or treat the many manifestations of CVD and thus would have a significant impact on personal and public health.

DESCRIPTION (provided by applicant): Simultaneous with the epidemic of obesity, there has been an epidemic of short sleep duration. Epidemiological studies have documented a link between short sleep duration and both obesity and obesity- related health problems including hypertension, diabetes, and mortality and basic laboratory studies have identified physiological mechanisms that may explain this association. However, to date, there have been no intervention studies examining the impact of changes in sleep duration on changes in body weight. The Center for Behavioral Intervention Development (CBID) proposed in this application seeks to translate the basic science on sleep duration into a novel intervention to reduce obesity and obesity-related co- morbidities. We propose a programmatic series of studies to develop a sleep + weight loss intervention. The target population for our studies will be young adults (age 25 - 45) where the association between sleep duration and obesity appears strongest, who are overweight or obese (BIVII 25 - 40), and who currently sleep less than six and a half hours per night. This series of studies will be used to examine the effects of increases in sleep duration alone and in combination with a weight loss program on eating and exercise behaviors (measured objectively), and ultimately on body weight. We will also examine the effects of increasing sleep duration on physiological, psychological and cognitive changes that may relate to the changes in eating and activity and adherence to weight control recommendations. The proposed CBID creates a new interdisciplinary team, including investigators in the areas of behavioral weight control, basic and clinical aspects of sleep, fMRI and neuropsychological assessment of cognitive function, eating and exercise behavior, and physiological changes associated with sleep and weight. RELEVANCE: Both obesity and short sleep duration are major health problems, with a variety of negative consequences. Given that short sleep may contribute to the problem of obesity, this proposal seeks to develop an intervention to increase sleep duration and to determine whether increasing sleep alone, or in combination with a weight loss program, can have positive effects on eating, exercise, and ultimately weight control. (End of Abstract)

DESCRIPTION (provided by applicant): Obesity is a major public health problem, with millions of Americans suffering from weight-related health complications, including Type 2 diabetes, coronary heart disease, hypertension, and osteoarthritis. Behavioral weight loss intervention has emerged as a key strategy in combating obesity and the associated health consequences. However, individuals differ in their degree of success in these programs and genetic factors are known to play a role. In this application, we propose to identify specific genes that predict individual differences in weight loss in response to behavioral intervention to help identify individuals who struggle with weight loss despite behavioral efforts. Specifically, we will determine whether obesity genes interact with lifestyle intervention in predicting weight loss at year 1 of the Look AHEAD trial (U01DK056992), an NIH-funded, multi-center randomized controlled trial with the primary goal of determining whether weight loss achieved through an intensive lifestyle intervention can reduce cardiovascular morbidity and mortality among persons with type 2 diabetes. At year 1, participants assigned to Intensive Lifestyle Intervention (ILI), focusing on changes in diet and physical activity, lost an average of 8.6% of their weight (N= 2,496;97.1% follow-up) relative to losses of 0.7% among individuals assigned to the Diabetes Support and Education (DSE) group (N= 2,463, 95.7% follow-up), who received diabetes support and education groups alone. Consent for genetic analyses was provided by 3,759 participants. Genotype data from the IBC chip, including over 4,000 markers within genes previously associated with obesity, will allow us to test our central hypothesis that genes that predispose to obesity interact with lifestyle treatment to influence weight loss following intensive lifestyle intervention. We conduct these aims with the explicit goal of bringing together a team with expertise in behavioral research, genetic epidemiology and molecular biology to create transdisciplinary researchers who are able to bridge across the disciplines and identify key gene x behavior interactions in the context of the Look AHEAD trial. PUBLIC HEALTH RELEVANCE: The interplay of genetic and behavioral factors is critical to understanding obesity and behavioral weight loss intervention has emerged as a key strategy in combating obesity. In this application, we propose to identify specific genes that predict individual differences in weight loss in response to behavioral intervention to help identify individuals that struggle with weight loss despite behavioral efforts.

DESCRIPTION (provided by applicant): Obesity is a major public health problem. Behavioral weight loss programs have been shown to be successful in reducing body weight and preventing the onset of medical complications of obesity. There is a need to develop cost-effective approaches to disseminating these weight loss interventions. This project evaluates an innovative approach to disseminating weight loss interventions. It uses a self-sustaining statewide program called "Shape Up Rhode Island", as a means of recruiting large numbers of participants to the program and combines this program with effective behavioral weight control strategies to improve the weight loss outcome. Shape-Up Rhode Island is a 12 week program to help Rhode Islanders lose weight and increase activity through an Internet delivered team-based competition, which recruited over 13,000 participants in 2009. To avoid markedly increasing personnel costs or participant burden, the Shape-Up Rhode Island program will be enhanced with a behavioral weight loss intervention including (1) education about diet, exercise and behavior strategies delivered via weekly multi-media behavioral lessons based on the Diabetes Prevention Program and Look AHEAD, that can be viewed by the participant on their computer;and (2) increased accountability through submission of weekly self-monitoring records and computer-generated individualized feedback. A pilot study of this enhanced intervention indicated that participants in Shape-Up RI adhered well to these added components and that the enhanced program significantly improved weight losses in the Shape-Up RI program. We propose to conduct a randomized controlled trial with 600 Shape-Up Rhode Island participants who will be randomly assigned to receive the 12-week standard Shape-Up Rhode Island program or an enhanced program, which includes not only the standard Shape-Up Rhode Island program, but also weekly video behavioral lessons and weekly automated feedback. The primary hypothesis is that the enhanced program will improve weight losses at week 12. Secondary aims are to compare the treatments on percent of participants achieving a 5% weight loss, on 6 and 12-month follow-up, and on behavior changes related to weight control, and to conduct cost-effective and cost-utility analyses comparing the two programs. This innovative intervention, which uses a statewide campaign for outreach combined with effective behavioral strategies for weight loss success, has the potential to be an important public health model for the treatment of obesity. PUBLIC HEALTH RELEVANCE: Behavioral weight loss programs can successfully reduce body weight, but these programs are available to limited numbers of overweight and obese individuals. This project evaluates a unique weight loss approach that combines a self-sustaining weight loss campaign (for outreach) with training in behavioral weight loss strategies and strategies to increase accountability (to improve weight loss success). This innovative combination has the potential to be a cost-effective model for disseminating weight control interventions.

DESCRIPTION (provided by applicant): Obesity is a major health problem, affecting over one-third of US adults. Behavioral weight control programs are the treatment of choice for mild and moderate obesity, but there is marked variability among patients in the weight losses achieved and the maximum weight losses are usually achieved by month 6, followed by weight regain. Both of these problems might be improved by a more specialized approach for the sub-group of obese patients who report a tendency to overeat in response to emotional and/or cognitive stressors, referred to as internal disinhibition. Recent studies show that approximately 50% of individuals entering behavioral weight loss programs report problems with internal disinhibition and that these individuals lose significantly less weight, particularly at 18 months, than other participants in standard behavioral weight loss programs. We hypothesize that these individuals might achieve better weight loss outcomes in a behavioral weight loss program that focuses on acceptance-based strategies rather than in a standard weight loss program. Acceptance based approaches teach patients to experience thoughts and feelings as they are, without attempting to control them and to continue to pursue their behavioral goals despite experiencing these negative thoughts and feelings, whereas standard behavioral programs teach patients to control their negative thoughts with techniques such as cognitive restructuring and distraction. Acceptance based approaches have yielded positive results for a variety of psychological and health conditions. In a pilot study we conducted, we obtained impressive results using an acceptance based behavioral intervention for obese patients who reported problems dealing with negative internal cues. We propose to conduct a randomized controlled trial comparing a standard behavioral weight loss treatment program (SBT) with an innovative approach that combines standard behavioral weight loss with an acceptance based behavioral intervention (ABBI). We will recruit 160 overweight/obese patients who report high internal disinhibition, and thus would be likely to benefit most from this novel approach to emotion regulation. These participants will be randomly assigned to 18 months of either SBT or ABBI with full assessments at baseline, 6, 12, and 18 months. The primary hypothesis is that participants in the ABBI program will achieve better weight losses than SBT at 6, 12, and 18 months. Secondary hypotheses are that participants in the ABBI program will report greater acceptance of negative thoughts and emotions and greater distress tolerance and will have better treatment adherence than participants in SBT, and that differences in acceptance of negative thoughts and emotions will mediate the differences in weight loss between the groups. This project uses an innovative approach to the treatment of obese individuals who report problems with internal disinhibition. Development of an approach that improves weight loss outcomes would provide a tremendous benefit to the field of obesity. PUBLIC HEALTH RELEVANCE: Obesity is a major health problem affecting over one third of US adults. Approximately half of the obese patients seeking help with weight control report problems dealing with negative thoughts and emotions and these individuals appear to do less well in standard treatment approaches. By incorporating strategies from a new treatment approach, in which patients are taught to accept these negative thoughts, rather than trying to change them, we may be able to improve the weight losses achieved by these obese patients.

DESCRIPTION (provided by applicant): This proposal is for competitive renewal of a T32 in Cardiovascular Behavioral Medicine research training at the Brown University Centers of Behavioral and Preventive Medicine (CBPM) and The Miriam Hospital. The program goal is to train a total of 13 postdoctoral fellows for two year periods to conduct research to reduce the burden of cardiovascular disease (CVD) by changing the most prominent lifestyle risk factors, including obesity, physical inactivity, and smoking. During our first four years of funding, we were extremely successful in recruiting 10 outstanding fellows and developing their independently funded scientific careers. All 5 graduates now hold faculty appointments and 4 of the 5 have their own NIH funding. The T32 develops researchers who advance the basic science understanding of the etiology of behaviors associated with CVD and who develop and disseminate effective interventions targeting these behaviors to prevent or treat CVD. Increasingly, our program focuses on translational research in which findings in basic science (e.g., genetics and neuroimaging) are used to inform behavioral interventions and dissemination research in which efficacious interventions are tested in community settings and with high risk populations. These approaches require multidisciplinary approaches which are facilitated by the ongoing collaborations between the CBPM and the Brown Department of Psychiatry and Human Behavior, the Department of Medicine and the Program in Public Health. There are large numbers of federally funded trials that provide outstanding research training opportunities for our fellows including projects on the effects of behavior change on CVD endpoints, studies of genetic and environmental contributions to health and CVD, and projects using innovative channels (e.g., Internet and text-messaging) and sites of delivery (e.g., YMCAs). We have retained and augmented our successful training model for this cycle, with Program Director Rena Wing, PhD, Associate Director Bess Marcus, PhD, and Administrative Director Justin Nash, PhD, continuing in their leadership capacity. Alfred Buxton, MD (Director of Cardiology), Jeanne McCaffery, PhD, and Anthony Spirito, PhD join the Training Committee. Training is highly individualized with all fellows developing core competencies in areas such as CVD-related behavioral research and specialized competencies in their specific areas of research. Formal didactics and mentored research experiences are combined to develop competencies. Mentoring teams are headed by a senior behavioral scientist and complemented with a physician or public health scientist mentor and a junior faculty mentor. Trainee progress in achieving training objectives is formally evaluated. Given our initial success and our ability to recruit highly competitive candidates, provide extensive research and training opportunities, provide outstanding mentors with established track records, and produce funded researchers and junior faculty members, we feel uniquely qualified to continue our T32 research training in behavior change and CVD.

DESCRIPTION (provided by applicant): The aging of the population and the epidemic of obesity have led to a rapid increase in the number of older, obese individuals with diabetes. Little is known about the long-term health effects of lifestyle intervention designed to lower weight and increase physical activity in this population. This application, which responds to RFA-DK-12-502, is submitted by one of the 16 clinical centers in the Action for Health in Diabetes (Look AHEAD) Consortium. All 16 clinical sites and the Coordinating Center have submitted parallel applications. This application proposes to continue the Look AHEAD clinical trial as an observational cohort study and to follow participants with new assessments of the health problems of greatest concern in older, obese individuals with type 2 diabetes. We will test whether random assignment to 9-11 years of intensive lifestyle intervention, compared to a control condition of diabetes support and education, results in improvements in 1) physical function, impairment and disability, 2) cognitive function and impairment, 3) diabetes control and microvascular complications, 4) late life depression, and 5) fractures and cancers. Secondary aims are to examine whether subgroup differences observed during the trial (which raised concern about possible unfavorable effects of intensive lifestyle intervention in those with a prio history of cardiovascular disease) endure and whether the excellent weight losses achieved in the intensive lifestyle intervention arm are maintained despite the absence of continued intervention activities. The Continuation will also support ongoing ancillary studies, maintain infrastructure for new ancillary studies, and sustain thorough analyses and publication of the data collected by Look AHEAD. We will continue to follow the Look AHEAD cohort (approximately 4,000 participants) across the 16 clinical sites. Participants entered the trial 9-1 years ago when they were obese or overweight and aged 45-76, and were randomly assigned with equal probability to either an intensive lifestyle intervention that has induced sustained weight loss and increased physical activity or control condition (diabetes support and education). Both arms have had excellent retention. Interventions were discontinued in Sept, 2012, but follow-up of the cohort continues. This application will fund one additional clinic visit and ongoing telephone-based outcome assessment. This application builds on the remarkable success of the Look AHEAD in inducing and sustaining weight loss and retaining participants. The planned continuation addresses important public health priorities for a rapidly growing and under-studied segment of the US population in a cost-effective manner, leveraging the extensive resources available from Look AHEAD.

? DESCRIPTION (provided by applicant): The first two years of life are increasingly recognized as a critical period for the development of obesity. Prior studies demonstrate the importance of parents in shaping this risk with particular emphasis on associations between maternal responsive feeding (i.e., higher responsiveness to child hunger and satiety cues and fewer assertive prompts to eat) and lower child BMI. However, research to date has been primarily cross-sectional, based on parent-report, and done almost exclusively in preschoolers or older children; longitudinal studies of mothers and toddlers that assess objective measures of responsive feeding within the context of antecedent and concurrent factors, are needed to better understand factors that promote responsive feeding and reduce long-term child obesity risk. We propose to enroll 156 mother-toddler dyads into a prospective study of feeding interactions and obesity risk, with assessments at 18, 24, and 36 months, in order to achieve the following aims: 1) understand factors related prospectively to responsive feeding between mothers and toddlers at 18 months; 2) determine whether responsive feeding at 18 and 24 months predicts change in zBMI and adiposity from 18-36 months; and 3) explore which factors are most strongly predictive of child zBMI change from birth to 36 months. Responsive feeding will be assessed with two home-based meal observations at both 18 and 24 months (total of 4). At these time points, mothers and toddlers will wear accelerometers to assess physical activity and sleep, and mothers will also complete three 24-hour dietary recalls of their own and their toddler's intake, and measures assessing additional maternal (e.g., perceptions of feeding practices and styles, dietary restraint) and toddler (e.g., temperament, appetite) factors that could influence maternal responsiveness and toddler obesity risk. Mothers' and toddlers' heights, weights and circumference/skinfolds will be measured at 18, 24, and 36 months. We propose to recruit participants from Healthy Beginnings (HB), an NHLBI-funded, two site randomized controlled trial testing the efficacy of a multi-component behavioral intervention in reducing risk of excessive weight gain during pregnancy. Half of HB participants were randomized to an intervention designed to reduce pregnancy weight gain, providing a unique opportunity to examine long-term effects on all of the above-noted study aims. HB also provides a unique opportunity to cost-effectively conduct this longitudinal study: participants are already being enrolled in HB; all are overweight or obese and 42 percent are Latina (important risk factors for child obesity); relevant assessments of women in HB occur at study entry (<16 weeks gestation), 22-24 weeks and 35 weeks gestation, and mothers and infants at delivery, 6 and 12 months. HB ends when infants are 12 months old. Extending follow-up through 36 months will enable understanding of longitudinal associations between early life influences on responsive feeding during toddlerhood, and prospective associations between responsive feeding and obesity risk. Findings will have important implications for preventive interventions during this important and understudied developmental period.

? DESCRIPTION (provided by applicant): This application seeks to follow the participants in Study of Novel Approaches to Weight Gain Prevention (SNAP) (Grant #U01-HL090864), a randomized clinical trial that has successfully reduced weight gain in young adults through 3 years. SNAP is the first weight gain prevention trial to show positive effects over an extended time period in this age group. The SNAP-Extension (SNAP-E) will cost-effectively determine whether the effects of the intervention can be maintained over 3 additional years (through a total of 6 years). Young adults, ages 20-35, gain on average 2 pounds per year, increasing their risk of developing obesity and obesity related co-morbidities. Previous efforts to prevent this weight gain have had limited success. SNAP is a randomized controlled clinical trial involving 599 participants, age 18-35 with a BMI of 23- 30, comparing weight changes over an average follow-up of 3 years in a control group and two innovative interventions. Both interventions are based on a self-regulation model, involving frequent self-weighing and changes in eating and activity if weight gain occurs. However, one intervention focuses on making small consistent changes in eating and exercise behavior to prevent weight gain; the other emphasizes periodic larger changes in eating and exercise, with a goal of producing a buffer against anticipated weight gains. SNAP has had excellent retention to date and has shown that both interventions significantly reduced weight gain relative to control through 3 years. Although weight changes in the two interventions do not differ from each other at 3 years, they have had very different weight change trajectories, raising questions about long- term efficacy. Continuing to follow these participants is critical to determine whether the skills imparted during these interventions and the resulting beneficial effects on weight gain are maintained longer term and whether there are differences in outcomes for large and small change approaches. In SNAP-E we will provide minimal intervention for the Small and Large Change groups using remote technology and will follow all participants at 6 month intervals using Smart Scales and on-line questionnaires. There will be one final clinic assessment at Year 6, with measures of body composition, cardiovascular disease (CVD) risk factors, dietary intake and objective assessment of physical activity, all implemented using procedures that were used throughout SNAP. The primary hypothesis of SNAP-E is that the magnitude of weight gain from baseline to 6 years will differ among the three arms. Secondary hypotheses compare the groups on dichotomous measures of weight gain, on CVD risk factors, and on weight control behaviors. Preventing weight gain may be a more effective public health approach than treating obesity. SNAP is the first study to show long-term benefits of an intervention on weight gain in young adults. Continuing to follow these participants in SNAP-E provides a cost-effective and unique opportunity to answer important questions about weight gain prevention.

? DESCRIPTION (provided by applicant): Over 25% of the US population >65 years of age have type 2 diabetes and 80% of these individuals are overweight or obese. These individuals face shortened lifespans, increased health care needs, greater medical complications, and lower quality of life relative to those of similar age without these conditions. Lifestyle interventions focused on weight loss are recommended for overweight and obese individuals with type 2 diabetes, but whether these interventions meaningfully improve the lives of older individuals with diabetes over extended follow-up is unknown. Look AHEAD is a randomized trial comparing the effects of intensive lifestyle intervention (ILI) focused on weight loss achieved through healthy eating and increased physical activity versus a control group given Diabetes Support and Education (DSE) in overweight and obese individuals with type 2 diabetes. Although ILI did not produce beneficial effects on the primary and secondary outcomes related to cardiovascular disease, it did produce beneficial effects on a broad spectrum of health parameters during the period of the intervention. The LA Extension (LA-E) will examine whether ILI, provided for 10 years during mid- life, has enduring benefits that persist beyond the period of the intervention for older individuals with diabetes. We propose to follow approximately 3,800 participants (current ages 58-89 years) for 4.5 additional years with biennial clinic visits and 6-month outcomes phone calls. The primary aims of LA-E are to test whether ILI relative to DSE has long term legacy effects on 1) increased lifespan and 2) reduced health care costs. Secondary aims test whether ILI relative to DSE has long-term effects on key dimensions of healthy aging: less frailty, reduced diabetic microvascular complications, and improved quality of life. LA-E will also compare long- term trajectories of weight, physical activity, fat and lean mass, and bone density and examine how these are related to outcomes. LA-E focuses on the clinical outcomes that are most relevant to healthy aging and resilience and will provide the long-term data needed to frame guidelines related to lifestyle intervention in the care of older overweight or obese individuals with type 2 diabetes.

PROJECT SUMMARY/ABSTRACT Behavioral obesity treatment produces clinically significant weight loss; for the greatest impact, it should be made available in the primary care setting where it can reach the many patients with overweight/obesity. We have developed a 3-month automated online behavioral weight loss program, Rx Weight Loss (RxWL), and shown that it produces clinically significant weight losses among primary care patients. Our early efforts at pragmatic implementation of RxWL have been promising, and have shed light on challenges associated with implementation, and the need to study longer-term effectiveness. We therefore propose to conduct a pragmatic study to improve the implementation and effectiveness of this behavioral obesity intervention delivered in routine and representative healthcare settings. We are partnering with the Rhode Island Primary Care Physicians Corporation (RIPCPC), a large primary care network of 58 practices with 100 physicians and 16 nurse care managers. Using the framework for Effectiveness-Implementation Hybrid Designs, we will simultaneously target effectiveness and implementation to maximize the public health impact of our research. We will randomly assign half of the 16 nurse care managers, and the practices they serve, to either Basic Implementation (alerts in the electronic medical record [EMR] to direct eligible patients to RxWL), or to the Enhanced Implementation (alerts, clinician skills training to motivate and support weight loss, clinician dashboard with reports on patient progress and tools to facilitate patient engagement and behavior change). We will test the hypothesis that the Enhanced Implementation will increase the proportion of patients directed to, enrolling, and completing the weight loss program. Because maintenance of weight loss is a critical problem, this project will also involve randomization of 600 patients with overweight/obesity and type 2 diabetes, hypertension, and/or hypercholesterolemia to the 3 month RxWL intervention followed by one of three maintenance conditions: (a) Control- 9 monthly online education sessions; (b) Monthly Lessons and Feedback- 9 monthly online video lessons teaching self-regulation with automated feedback on the self-monitoring record; (c) Refresher Campaigns- 9 monthly on-line video sessions, teaching self-regulation and providing two 4-week courses with novel strategies and behavioral challenges to improve long-term outcomes. We will test the hypothesis that 12-month weight losses are better with Refresher Campaigns than Monthly Lessons and Feedback, and both are better than Control. Secondary outcomes include changes in weight, CVD risk factors, and medication use over a full 24 months. Our project is significant and innovative because: it uses an empirically validated approach to obesity treatment that is integrated into the primary care setting, leveraging existing staff and EMR capabilities; it has a dual focus on improving effectiveness and implementation; it has a pragmatic design in partnership with a large primary care network that treats a diverse patient population; and it has potential to it provides a scalable, sustainable approach that can serve as a model for broader dissemination of obesity treatment intervention.