Robert F. Leeman, Ph.D. - US grants

DESCRIPTION (provided by applicant): The proposed study is designed to assess the predictive utility of six primary risk factors for alcohol-related problems in a sample of 300 first-year undergraduates. Dependent variables to be assessed include drinking behavior (i.e., frequency and quantity of use) and alcohol-related problems. The six primary independent variables (risk factors) to be tested are family history of alcohol and drug abuse, friends' drinking pattern, stress (i.e., life events and daily hassles), perception of risk associated with alcohol use, valence of initial experience(s) with alcohol and drinking-induced disinhibition. All variables will be assessed through the use of a confidential questionnaire. As part of the proposed study, a scale designed to measure drinking-induced disinhibition will be constructed. Preliminary data suggests that this scale measures three types of drinking-induced disinhibition and two categories of effects related to disinhibition. Participants will be randomly assigned to one of two conditions: 1) completion of this and an unrelated questionnaire or 2) an open-ended interview followed by completion of the alcohol questionnaire only. The aim of the interview is to explore stability and change in students' drinking patterns over time and to serve as a validity check for the variables listed above. For the prospective component of the study, participants will be brought back one year later to complete a brief version of this questionnaire. There are two goals of the proposed study: to identify risk factors associated with alcohol-related problems in order to properly identify individuals who may be at risk and to determine which personal characteristics should be the target of intervention efforts.

DESCRIPTION (provided by applicant): This application is for a "Mentored Research Scientist Development Award" (K01). The candidate, Robert Leeman, Ph.D., has a programmatic interest in high-risk alcohol use and difficulties with self-control, with a particular interest in the young adult population. Dr. Leeman aims, as a junior faculty member at Yale, to acquire skills to develop into an independent scientist in the field of alcohol research. The training and research plan enlists the mentorship and collaboration of Stephanie O'Malley, Ph.D., Professor of Psychiatry, the Director of the Division of Substance Abuse Research and the Clinical Core of the Yale Center for the Translational Neuroscience of Alcoholism (CTNA) and Marc Potenza, M.D., Ph.D., Associate Professor of Psychiatry and the Child Study Center and Director of the Yale Program for Research on Impulsivity and Impulse Control Disorders. The mentors-along with consultants, all of whom have international reputations in their fields-will assist Dr. Leeman in accomplishing his training goals, in completing the projects detailed in the research plan and in his progression toward becoming an independent researcher. Dr. Leeman's primary training goals for the K01 are 1) to enhance his skills in conducting alcohol administration research and 2) to develop specialized skills in data analytic techniques to model latent variables and to analyze prospective data. A secondary training goal is to learn more about the neurocircuitry implicated in trait and alcohol-induced disinhibition as well as the long-term alterations of neurocircuitry that typify alcoholism. The Research Plan consists of three interrelated studies that relate to Dr. Leeman's interests in alcohol use and self-control and will allow him to apply knowledge gained from the training proposed in the award: 1) testing structural equation models to assess associations among trait disinhibition, expectancies of alcohol's disinhibiting effects and impaired control over alcohol use and to assess these constructs as cross-sectional predictors of high-risk drinking;2) a secondary data analysis to test disinhibition expectancies and impaired control over alcohol use as mediators of outcome in a clinical trial of naltrexone and BASICS counseling for heavy drinking reduction in young adults and 3) development and validation of a human alcohol self-administration paradigm designed to model impaired control over alcohol use. The proposed alcohol self-administration paradigm entails provision of disincentives for non-moderate alcohol use that disregards a controlled drinking guideline. The proposed research has the potential to inform our understanding of the ways in which various difficulties with self-control contribute to high-risk drinking. Results from the proposed research will provide preliminary data for an R01 application to be completed by Dr. Leeman during the award period. Completion of the proposed training and research would allow him to transition to independence as an investigator by the completion of this award and lay the groundwork for his long-term career goals. PUBLIC HEALTH RELEVANCE: Young adult heavy drinking is a significant public health concern. The candidate for this award requests training and proposes a research plan to progress toward independence as an investigator with focus on risk factors for and mechanisms underlying heavy drinking and alcohol-related problems in young adults. Knowledge about risk factors and underlying mechanisms can inform intervention approaches to reduce heavy drinking and alcohol-related problems in this population.

DESCRIPTION (provided by applicant): Young adult heavy drinking is a public health concern. Young people drink alcohol frequently, which puts them at risk for injuries, accidents and subsequent alcohol dependence. Due to strong contingencies supporting their alcohol use and limited motivation to change, young adult drinkers are a challenging population to treat. Current behavioral interventions are efficacious overall but effect sizes have been modest. Given these factors, new interventions are needed to target cognitions and behaviors that support young adult heavy drinking. Dual process models posit that addictive behaviors stem from failed attempts at inhibiting impulses and overactive automatic, appetitive, approach tendencies. Current behavioral interventions typically aim to enhance young adults' inhibitory control over excessive drinking by prompting effortful behavior change. In contrast, automatic, approach tendencies have been ignored largely in behavioral interventions. Findings of strong automatic approach tendencies among heavy drinking young adults suggest that an intervention to reduce these tendencies may be well-suited to this population. Automatic action tendency retraining (Wiers et al. 2010; 2011) is a theoretically-supported, novel intervention with promising initial empirical support. The retraining procedure entails pushing away motions with a joystick in response to alcohol images over repeated trials. In the proposed study, automatic action tendency retraining will be compared to a control condition in heavy drinking young adults (N = 72), using a novel, naturalistic alcohol self-administration model of impaired control over alcohol use (Leeman et al. 2012). Impaired control is a deviation from a conscious attempt to limit alcohol use that may occur due to strong automatic approach tendencies toward alcohol. Notably, the impaired control paradigm creates disincentives for drinking alcohol excessively, providing participants with reasons to limit alcohol use. Excessive alcohol use in this paradigm ignores a guideline for moderate use and occurs despite possible negative consequences, thus modeling key elements of problem drinking. We hypothesize young adults randomized to automatic action tendency retraining will drink to significantly lower peak estimated blood alcohol concentrations and consume fewer drinks overall than those randomized to the control condition. Exploratory comparisons will also be made between the experimental retraining and control conditions on measures of drinking topography including mean time taken to consume each drink. Findings from this study will inform future clinical trials to test the efficacy of automatic action tendency retraining for young adult heavy drinkers. Results of the proposed study will also inform subsequent research to combine the retraining procedure with an intervention to enhance inhibitory control. Theory and evidence suggest automatic/implicit and effortful/explicit interventions contribute uniquely to alcohol use reduction, making their combination promising.

? DESCRIPTION (provided by applicant): Protective behavioral strategies (PBS) are techniques used to limit alcohol use and/or curtail related negative consequences. While PBS use is generally associated with more moderate drinking, some strategies may have stronger protective effects than others. These findings along with mixed results from studies of PBS- focused interventions suggest there may be limitations in the ways counselors have taught PBS and/or ways young adults implement them. Limited use of concrete tools to facilitate PBS use may be one such limitation. Technology-based tools (TBTs) have 2 advantages for PBS use: 1) young adults are interested in technology for health purposes; 2) they are skilled at technology use. Smartphone applications (apps) are promising but under-researched. Apps that facilitate lowering of blood alcohol content (BAC) would be particularly valuable. We will compare 2 BAC monitoring apps with a phone-based drink counting control condition as adjuncts to BAC-focused counseling for efficacy in reducing alcohol self-administration. One app is a breathalyzer that produces accurate readings using a device that snaps onto a smartphone. A second app yields BAC estimates based on sex, weight, time elapsed and number of drinks. While the breathalyzer app provides high accuracy, some young adults could be self-conscious about blowing into a device. Between-subjects, we will randomize heavy drinking young adults (N = 99) to brief counseling plus 1 of 3 TBTs (breathalyzer, BAC estimator, control condition), which they will use during a 3-hour laboratory alcohol self-administration period. Pay reductions based on poor performance on cognitive/psychomotor tasks sensitive to alcohol effects provide a disincentive for excessive drinking during the drinking session. Participants may avoid pay reductions with help of a TBT. Peak estimated BAC and number of drinks consumed during the 3 hours will be the primary outcomes. After the drinking session, participants will be given all 3 TBTs to use on their own in the field for 2 weeks to assess alcohol drinking while each TBT is used; preference for and acceptability of each TBT as exploratory aims. Laboratory alcohol self-administration paradigms, while used often to test medications, have been under- utilized in testing behavioral interventions. Lab paradigms offer advantages in the study of PBS, including direct measurement of PBS use and its relation to alcohol consumption with reduced emphasis on self-report. We hypothesize that participants randomized to either BAC-related app condition will administer significantly fewer beers and reach lower peak estimated BAC in an alcohol drinking session, compared to a drink counting control condition. We will also compare the 3 TBTs on participants' ratings of acceptability and likelihood of future use between-subjects, based on their experiences during the session and within-subjects, based on their experiences during the 2-week field use period. We will also test for interactions by sex for all outcomes. BAC-related apps could lead to large decreases in drinking with minimal effort. Potential public health impact is substantial due to prevalence of alcohol use disorders and infrequent treatment seeking in this population.

PROJECT SUMMARY The rate of new HIV infections remains unacceptable, particularly in Florida and among men who have sex with men (MSM). Black and Hispanic/Latino, as well as young adult MSM are at particularly high risk, due in part to overlapping risk behaviors like heavy drinking. Alcohol use increases unprotected sex and reduces treatment adherence, making combined alcohol and risky sex prevention optimal. New preventive efforts for HIV and alcohol are a high priority area for NIAAA and must be targeted to these highest-risk groups. The goal of this UH2/UH3 project is to develop and test initially a synergistic, mobile intervention that will reduce alcohol use and risky sex and prevent HIV infection among the highest-risk individuals. The proposed intervention combines brief motivational intervention; daily monitoring via interactive voice response (IVR) with personalized feedback; and pre-exposure prophylaxis (PrEP). Combining them offers the strengths of all 3 while compensating for limitations of each, yielding a combined intervention with great potential impact. Based on theory and prior evidence, we hypothesize that this combined preventive intervention will be associated with greater alcohol use reduction and medication adherence than a standardized educational control condition. This project is innovative in that this combination of 3 efficacious interventions has not been tested to reduce alcohol use and HIV risk. Further, there are no established interventions to enhance PrEP uptake/adherence and no studies have provided intervention targeting both alcohol and PrEP uptake/adherence. In the UH2 phase, we will recruit MSM ages 18-30 who report HIV-negative status for a web survey (N=683) to yield normative data for the personalized feedback intervention component and focus groups (N=30) to provide input on the initial version of the intervention. Based on the web survey and focus groups, the intervention will be modified and tested in a preliminary usability study (N=10) to prepare for the UH3 phase. Completing each benchmark of the UH2 phase indicates feasibility of the UH3 intervention study. For the UH3 phase, we will recruit higher-risk MSM (N=80) for a 30-day study to test the combined mobile alcohol and HIV preventive intervention. All participants will receive open-label PrEP and complete a 5-minute daily IVR assessment of alcohol/substance use, sexual behavior and PrEP taking. Participants randomized to intervention will get brief web-based alcohol and HIV prevention followed by IVR monitoring including personalized feedback. The web- based component is designed to increase risk perception and motivation to change while the IVR component will enhance PrEP adherence and bolster risk perception and motivation further. Participants randomized to control will get standardized education, not personalized intervention, and give IVR responses for assessment purposes only with no feedback. Follow-up will occur at the end of the 30-day intervention and 6-months post- treatment. This project represents an early step in developing and testing a cost-effective, scalable preventive intervention that will be readily accessible, even to rural and lower socioeconomic status individuals.

Creation of a new T32 program in Florida, focused on alcohol and HIV infection, will fulfill a significant need. The state of Florida currently ranks first in new HIV infections per year, second in total HIV/AIDS cases, and third in total US population. Alcohol consumption contributes to poor HIV outcomes and to ongoing HIV transmission, and the relationships between alcohol consumption and HIV can vary by age, gender, ethnicity, and sexual orientation. The University of Florida is an ideal location to host the proposed T32, not only due to its geographic location and access to diverse populations, but also due to our growing NIH-supported alcohol research and infrastructure. The overall objective of this T32 grant is to train and mentor the next generation of researchers who have the skills, knowledge and experience to improve health outcomes in those affected by alcohol and HIV. We need a research task force that is capable of developing and implementing alcohol intervention across diverse populations, who can use novel data systems and sources, and who seek to reduce comorbidities associated with aging. Thus, the specific aims of our training program are to a) deliver an academic curriculum, b) provide outstanding mentoring, c) ensure skills in communication of science, d) provide experience in team science, and e) maximize professionalism and ethical conduct of research. The training program will support up to four pre-doctoral and two post-doctoral trainees at any given time, and several potential candidates have already expressed interest. Trainees will be based in the following academic programs: Epidemiology, Biostatistics, Clinical and Health Psychology, Nursing Science, Health Education and Behavior, and/or the Interdisciplinary Program in Medicine. These programs represent a broad range of health- related disciplines, ensuring trainees will have state of the art training in team science. Our 18 faculty mentors span four colleges and eight departments at UF. Each bring unique skills and expertise related to alcohol and HIV. The training program will ensure appropriate depth in knowledge regarding alcohol, HIV, and three additional focus areas that represent areas of strength in ongoing research at UF: a) health behavior intervention science; b) epidemiology and data science; and c) cognitive science related to aging. The training program will be closely integrated with Southern HIV Alcohol Research Consortium (SHARC), which is supported by over $10 million in ongoing NIAAA funding through 2021. The T32 will be led by three MPIs who each have specific administrative roles, and who will obtain input from an Internal Steering Committee, an Advisory Council, and ongoing program evaluations. UF is an outstanding training environment with many supporting resources, including a pledge to provide an additional $500,000 in overall support to our specific training program. Ultimately, the impact of the training program will be judged by the long-term track record of trainees who complete the training program, which we will monitor over time.

PROJECT SUMMARY Young adult drinking is a public health issue. Current interventions yield small effect drinking reductions, thus, new approaches are needed. Smartphone applications (apps) have great potential for drinking moderation. Almost all young adults own a smartphone and most are open to technology use to moderate drinking. Though there are many moderate drinking apps, quality varies and there is no evidence any are more efficacious than a control condition for young adults. Thus, there is a knowledge gap as to which apps may be helpful. Brief interventions have shown personalized feedback based on motivational interviewing (M.I.) has efficacy, but these interventions give feedback about general patterns only, not drinking and impairment in the moment. Theory and evidence emphasize that slowing pace of drinking is difficult. These findings suggest young adults need additional help, preferably while drinking, to slow their pace of alcohol use. Apps have great potential for needed in-the-moment intervention. There are no efficacious, in-the-moment behavioral interventions for young drinkers. Human laboratory studies support perceived impairment as a focus of an in-the-moment, moderate drinking app. Two studies using different cognitive tasks (including a driving simulator) found heavier drinking young adults underrate impairment more than light drinkers. Simulated driving results in particular suggest serious consequences from misperceived impairment. An app that provides accurate feedback on impairment could increase perceived impairment and reduce drinking. This study will test an app providing in-the-moment feedback on impaired inhibitory control as an adjunct to an existing, M.I.-based, brief web-based intervention that gives feedback on overall drinking. App feedback will be tied to performance on the cued go/no-go task, which tests ability to respond quickly to ?go? targets (activation) while withholding responses to ?no-go? targets (inhibition). Moderate doses to blood alcohol content (BAC) .05-.06% reliably lead to inhibition errors, but higher doses are usually needed for ?go? reaction time (RT) to slow. Thus, ability to respond remains but ability to inhibit is impaired, which has negative implications. Using M.I.- consonant language, feedback will compare RT and inhibition failures after alcohol to RT and errors pre-drinking. The experimental app, which will be derived from a larger app in a current study, will be compared to 2 control conditions in which the task is completed without this novel feedback. Heavy drinking young adults (N=99) will be randomized to 1 of the 3 app conditions; dosed to BAC=.06% in small groups in a bar lab; then use the experimental or control app, followed by opportunity to self-administer more alcohol. Primary outcomes will be differences between study conditions on BAC and alcohol self-administered. During a 4-week period post-session, all participants will use the experimental app in actual drinking situations for 2 of the 4 weeks, enabling within-subject comparisons of drinking with vs. without the app. This study will yield preliminary data for an R01 to test concurrent use of multiple mobile tools (e.g., smartphone breathalyzer, wrist sensor) for combined efficacy in reducing drinking.

PROJECT SUMMARY Alcohol misuse in people living with HIV (PLWH) is a public health issue given relationships to cognitive and physical effects, which may subsequently accelerate HIV progression, increase likelihood of transmission and hasten related comorbidities. Thus, efficacious interventions to reduce alcohol use in PLWH are needed. Specifically, contingency management (CM; tangible reinforcement to change behavior) has been efficacious for alcohol intervention in the general population, but there are no published studies focused on testing CM for alcohol misuse in PLWH. Our current project testing 30-day CM including a subsample of PLWH (U01 AA020797) has promising preliminary findings. Despite its efficacy, remaining concerns about CM typically relate to long-term feasibility given financial costs or the possibility that negative behaviors will return when reinforcement ends. Thus, there is a need for approaches to extend CM beyond a limited period and make this approach amenable to wide dissemination. In this proposed P01 component project (N=120), we will implement several innovations to address feasibility concerns with an eye to research using implementation science methods in community health centers and clinics. Our novel approach will marshal mobile health (mHealth) capabilities, alcohol biosensors and gamification, which may enhance engagement through social connections and friendly competition. We will extend our current CM research by enrolling a wider range of participants regarding drinking behavior, age and comorbidities in a 30-day CM induction period. Bio- confirmation will be based on smartphone breath alcohol readings with identity confirmation. Our findings indicate the majority of PLWH avoid heavy drinking for at least 30 days with CM but a considerable minority do not, making prediction of outcome based on key baseline characteristics important. After 30 days, participants will be engaged in a motivational interview (MI) including personalized feedback based on reductions in alcohol use, enhanced cognitive and/or physical functioning. Following the 30-day CM induction and MI, responders will be randomized to 1 of 3 conditions to inform progress toward disseminable CM: 1) CM with intermittent reinforcement, plus novel, mHealth-based gamification; 2) CM with intermittent reinforcement without gamification; 3) or non-contingent reinforcement (control condition). In this innovative, second 30-day period, reinforcement will be based on wrist biosensor not breath alcohol readings and on a weekly rather than daily basis including reinforcement for bio-confirmed drinking moderation, not only abstinence. Follow-up will occur at 60, 90 and 180 days. Primary aims will test the magnitude of increases in percent days abstinent during the 30-day CM induction and baseline predictors of outcome (e.g., drinking severity, executive function). We will also test alcohol abstinence as a predictor of cognitive, biological and HIV outcomes. In addition, we will compare acceptability and preliminary efficacy across the 3 study conditions during the second, 30-day CM period. This project is an initial step to implement affordable, technology-based CM for alcohol in PLWH.