Stephen A. Maisto - US grants

The major long-term goal of the proposed research is to prevent and reduce the costs in human suffering and fiscal resources that are associated with excessive alcohol consumption, through the use of brief intervention (BI). Another long-term aim is to explain changes in alcohol use that occur with or without the aid of formal treatment. The specific aim of the research are to: (1) investigate the effectiveness of two BIs for alcohol problems, advice and motivational enhancement, that are delivered in family practice and general internal medicine clinics; (2) investigate patient pretreatment stage of change regarding alcohol use as a moderator of the main effects of BIs on alcohol consumption outcomes; (3) investigate patient factors as overall predictors of Bl alcohol consumption outcomes in primary care clinics. The major predictors evaluated will include gender, coping skills, and severity of alcohol dependence; and (4) explore the mechanisms of the effectiveness of BIs. Subjects will be 244 men and 244 women 21 years of age or older who are primary care patients at five clinic sites. Eligibility for the study will be determined by initial telephone screening and in-person baseline assessment. Following the baseline evaluation subjects will be randomly assigned to one of 3 intervention conditions, advice, motivational enhancement, or standard care control. The BI will occur shortly after the BL assessment. Follow-up assessments will occur by phone (1,3 months) or in person (6,12 mo.) and will include multimethod measures of substance use, alcohol and nonalcohol related service utilization, treatment-related factors, and health status and medical services utilization. Collaterals will be interviewed by phone about the subject's behavior at all assessments. The proposed study is significant for its potential to refine the use of a treatment approach that could save billions of dollars through limiting or preventing adverse consequences of heavy alcohol use. The study also will further the understanding of change in drinking behaviors.

DESCRIPTION (adapted from the Abstract): Current rates of infection with HIV have been increasing among heterosexuals and women. Young adults seem to be especially at risk for HIV infection. The long-term goal of this research is to explain the relationship between the use of alcohol and the occurrence of HIV risky sex among young adult heterosexual men and women. Such knowledge is seen as essential to improvement of prevention interventions for reducing the incidence of HIV infection. The short-term aims of this research are: (1) to use formative research procedures to refine and develop role-play scenarios as part of the measurement of behavioral (condom use negotiation) skills in men and women; (2) to assess the effects of alcohol and person variables on risk perceptions and behavioral skills in young adult heterosexual women; (3) to extend the previous aim by including young adult participants of both sexes, multiple doses of alcohol, and a measure of information processing as part of the assessment protocol; and (4) to conduct exploratory path analyses of data from both experiments following a partial mediation model of the effects of alcohol on the occurrence of risky sex. The formative studies refining existing role-plays will include 30 heterosexual young adult men recruited from the community. Formative studies used to develop role-plays targeting women will include 35 heterosexual young adult community women. The resulting role-plays will be used as measures of behavioral skills with participants in the two experiments. In Experiment #1, 102 young adult heterosexual women will be assigned randomly to receive alcohol (BAC =.08%), placebo, or water in their second experimental session. The first session will include the measurement of several person variables. The primary dependent variables in this study will be perception of risk involved in engaging in risky sexual behaviors, and behavioral skills. Experiment #2 will include 128 (64 women, 64 men) heterosexual persons. It will extend the first experiment by including random assignment to low alcohol dose condition (BAC =.04%), and the inclusion of a divided attention task.

DESCRIPTION (Provided by applicant): This application requests support for (KO2) Award for Stephen A. Maisto. His overall career goal is to contribute to the advancement of knowledge about alcohol treatment through the achievement of three specific career goals: (1) to advance his progress in becoming a leader in the scientific study of outcomes and mechanisms of interventions for alcohol problems, (2) to increase his expertise in the study of new statistical methods and accompanying computer technology that are becoming important in intervention research, and (3) to continue to mentor junior colleagues. This proposal describes two currently funded projects that are part of the research plan. Project 1 has two substudies designed to evaluate the effectiveness of an enhanced brief motivational intervention (BMI) for binge drinking in college students. In substudy 1, participants identified as binge drinkers are randomly assigned to receive a basic BMI, an enhanced BMI that adds a decisional balance exercise, or an assessment only control group. Substudy 2 replicates the first substudy but is done with individuals presenting to a campus substance abuse counseling program. All participants provide data on drinking and related problems at 1, 6, and 12 months post-intervention. Project 2 is designed to investigate subject reactivity to assessment protocols. Participants will be recruited from an outpatient AOD treatment service and will be randomly assigned to one of four conditions formed by the combination of frequency and Comprehensiveness of assessment. Participants will be evaluated at admission to treatment and over the course of 1 year. These and, future research projects form part of the applicant's program of research and is dedicated to the study of the effectiveness of BIs for alcohol problems and the mechanisms of their action. The applicant's career development plans and include acquiring knowledge of new developments in statistical methods, continuing mentoring of junior colleagues, and continuing the conduct of programmatic research. The K02 award would allow the applicant protected time to continue to develop his skills in and to conduct a program of research on alcohol treatment.

(Revised Abstract) DESCRIPTION (provided by applicant): Men who engage in risky behavior have been most affected by the HIV/AIDS epidemic in the US. Furthermore, data suggest a recent upsurge in risk taking by such men, especially among individuals in the young adult age range. The long-term goal of this application is to advance understanding of alcohol intoxication as a determinant of risky behavior among young adult men on a given occasion. Understanding the influences of alcohol intoxication as part of a complex of variables is essential to enhancing the effectiveness of HIV prevention interventions. In this regard, HIV prevention interventions are not likely to be effective without knowledge of the determinants of risk behavior. This is especially critical among a population vulnerable to HIV that is experiencing a resurgence of new infections following a period of decline. The main short-term goals of this research are as follows: (1) To use formative research methods to (a) create two role-play scenarios that will be used as vehicles to measure risk exposure, negotiation skills, and intentions to engage in risky behavior and delivered by CD-ROM interactive video, and (b) select a sample of film clips that will be used in the proposed experiments; and (2) to conduct an experimental study of the effects of beverage administration and other factors, and has interaction as dependent variables relevant to the antecedents of safer behavior according to prominent theories of HIV prevention. The formative studies conducted to develop the role-plays will include 40 young adult men, and a total of 35 men will be recruited to help select the film clips. The experimental study will follow the conclusion of the formative studies. In the experiment, 184 young adult men will be assigned randomly to one of eight conditions formed by the combination of beverage administration (water control, placebo, low alcohol dose [BAC = .04%], or moderate alcohol dose [BAC = .08%]) and other factors. The primary dependent variables will be risk perception, risk exposure, negotiation skills, and intentions to engage in risky behavior.

DESCRIPTION (provided by applicant): This is a revised competing continuation Senior Scientist Research and Mentorship Award (K05) application for Stephen A. Maisto, Ph.D. The primary goals of this application are to advance my research programs in (1) alcohol and other drug assessment and treatment research methods, (2) alcohol treatment outcomes, process, clinical course, and relapse, and (3) human alcohol challenge research, to continue to explore statistical methods and techniques of longitudinal research that may be applied to advance knowledge about alcohol treatment outcomes, mechanisms of treatment-related change, alcohol treatment clinical course, and relapse, and to add to my success in mentoring junior investigators and postdoctoral ferllows. The renewal of my K05 award would allow me to continue to pursue these primary aims at the high level of activity that has characterized the period of my current K05 award, which ends on 8/31/13. During the K05 award period, I propose to continue my research program in the research areas noted above and that is based in Syracuse University and in collaboration with colleagues at SUNY Upstate Medical University (Syracuse, NY), the VA Medical Upstate NY Network, and at other institutions in the US. My Mentoring Plan made feasible by the K05 award includes the addition of four new mentees, three Ph.D.s and 1 M.D.-Ph.D. As I have done successfully since the beginning of my current K05 award, I intend to maintain a cohort of an average of 4 junior investigator and postdoctoral fellow mentees for each year of the K05 award renewal period.

The following modified versionofthe original application's Abstract gives a succinct description of the proposed researCI:l: ', This application'slong-ferl11'goal is toenharice the effectiveness of AUD relapse prevention interventions lhroughadVaricing understanding of the relationships among interpersonal stress, affect regulation, alc()hollapse, 81ld pat~erns of alcohol 'usefoHowing AUD treatment. This qpplicatipnha? two major aims: (1) To investigate the association ofAgonistic$triving (defined as a 'preoccupationwithpersonalgpalsthat involve controlling, managing, ordomiqating other 'people), affect regulation, and their interaction, with time to first lapse,and overallalcohpl use, " respectively, and (2)To investi!:jate the role of interpersonal events as mediatprs of the relationship , among Agonistic Striving, affect regulation, andi3lcohol consumption in the second and third monthspost-treatrnent. The application also has 2 exploratory aims that concern the investigation of cardiac vagal tone (Vagal tone 'isthought to reflecttheabiiitytoniaintain hOJl1eQstasis)as a 'possipleindicator of affect regulation,and the relationship among Agonistic Strivi'lg, affect , regulation, and the content of perceived lapse preCipitants, fflspectively. In this study, 156 men and women,admitted to AUD h1patient treatment will be assessed at treatment entry on their alcohol 'use and related functioning, the Social Cqmpetence Interview, and Anger Transcendence Challenge. The Social Competence Interview and Anger Transcendence Challenge wiU provide . self-report, behavi()ral, and physiological data on affective responses tointerpersbr18lstressors and are the sources:of measures of Agonistic Striving and affect regulatibn,respectively. The - . assessment protocol \3lso Will include measurement of the perceivedstressfulness of interpersonal events in thenaturalenvironmentthrough the collection 6fecological momentary assessment data, . Which will be obtained by use of Interactive Voice Response technology;The eCQlogical . . momentary~ assessment will occur for 4 weeksfcillowing treatment discharge. participants will. be re'-assesseq oil their alcohol use, alcohoUapses, and relClted information biweekly following [unreadable] treatment discharge over the course of12weeks. Additionalvariables related to alco~oluse ahd relat~d functioning wHl be reassessed at6 and 12 weeks. . . . In the proposed two-ye.ar version ofthis study;the specific aims will[unreadable] not change. In effect, we propose toaccomplish~he same aims with a sample size reduced by about 28 percent (newN= 156)~Given the research design of this study, the time difference will pose little difficulty;[unreadable] it simply will be a matter ofending patient recruitment earlier than we had planned origirially.On the other hand, we Will. nof have to reduce recruitment by half (2 years of fundingasopposed to 4), because We will be. able to hi.re additional research st~ff to accelerate participant recruitment rate to achieve . a sample-size thafis72percentoJ the originally proposed N= 216. Note that the proposed budget forYear 1 and Year 2 ofARRA funds reflects the hiring 'ofmorestaffthan originally proposed for the4-yearprotocolsothat recrui.tment can be accelerated. We expectsuffident patient flow Citthe . clinical site of participalitrecruitmenUo achieve this accelerated recruitment rate. We estimate that the revised sample size will allow sufficient power to detect medium effect sizes _ of interest. In this regard, the original application's proJectedsample size requirementswere conservatively based on small-medium effect size estimates, and calculations, even at that, showed power equal to 1.00 for [unreadable] 'Some of the effects tested;We expect actual critical effect Sizes closer to medium magnitude.

DESCRIPTION (provided by applicant): The establishment of a therapeutic alliance between the patient and therapist is generally viewed as a central component of the behavior change process in the treatment of alcohol use disorders (AUDs). However, the majority of research serving as the basis for this conclusion has been descriptive. At this juncture, a transformative, next-step awaits the field - specifically, the development and evaluation of a contemporaneous, session by session feedback and guidance system for enhancing the therapeutic alliance in the service of improving treatment process and, ultimately, outcomes. In the proposed study, the participants will be alcohol dependent patients entering outpatient AUD treatment. Each will participate in a structured, 12- week treatment regimen of weekly individual treatment sessions. After each session, patients will complete the short form of the Working Alliance Inventory (WAI), which measures patients' perceptions of the therapeutic alliance. Two treatment conditions will be evaluated. In the experimental condition, feedback and guidance regarding the patient's reports on the therapeutic alliance will be provided to the therapist following each treatment session attended (Feedback condition). The feedback specifically will entail descriptive information on the patient's perceptions of the alliance as well as techniques and strategies that could be used by the therapist in service of enhancing the alliance or maintaining already strong alliances. In the usual treatment condition, no feedback on the therapeutic alliance will be provided to the therapist (No Feedback condition). Comprehensive research assessments will be conducted with patients at baseline, end of treatment, and at 3-, 6-, 9-, and 12-months post-treatment. The project's specific aims are three-fold. The first aim is to test the effects of providing feedback and guidance to therapists regarding patient perceptions of the therapeutic alliance on overall, patient-provided therapeutic alliance scores (averaged across treatment sessions attended during the 12-week treatment regimen). The second aim is to test the effects of providing feedback and guidance to therapists regarding patient perceptions of the therapeutic alliance on alcohol involvement (operationalized as percent days abstinent and drinks per drinking day) (a) during the treatment period and (b) during the 12-month follow-up period. The third aim is to test overall, patient-provided therapeutic alliance scores (averaged across treatment sessions attended during the 12-week treatment regimen) as a mediator of the proposed relationship between Feedback condition and alcohol involvement during the 12-month follow-up period. Positive results associated with providing therapists with feedback on patient perceptions of the therapeutic alliance would represent an important advance for the field. Furthermore, there would be direct transportability of the feedback technology being evaluated in this study to community settings.

DESCRIPTION (provided by applicant): This proposal focuses on two aims of PA-11-006: Substance Use and Abuse, Risky Decision Making and HIV/AIDS: 1) How does substance use shift the contribution of explicit (effortful) versus implicit (automatic) processes in decision-making about HIV-risk behavior, and 2) How do laboratory methods and simulations relate to real world risky behavior? The study incorporates an innovative pairing of an alcohol administration experiment with a subsequent experience sampling (ESM) study to test the external validity of the laboratory results. Interventions designed to reduce HIV risk behavior frequently focus on educating people about risks, increasing their motivation to avoid risks, and improving skills congruent with healthy choice. However, there are considerable gaps in knowledge about the processes involved in risky choice during the heat of the moment. Incorporating research on automatic processes, implicit cognition, and associative memory into the study and prevention of health risk behaviors is an important and largely unrealized opportunity for improving public health (Stacy et al., 2010). Automatic evaluations and approach biases can be successfully retrained via conditioning, resulting in corresponding changes in behavior (Chen & Bargh, 1999; Houben et al., 2010; Wiers et al., 2010). Research in diverse fields supports a dual-process model of self-control. Such models posit that self-control consists of two dimensions, a fast acting, reflexive, automatic dimension and a slower acting, deliberative or effortful dimension (Lieberman, 2007; Wiers et al., 2007). Automatic, reflexive, control emphasizes affective processes, while the effortful control dimension may consist largely of higher-order executive control processes (Lieberman, 2007). Risky sexual behavior may result when the strength of automatic approach behaviors exceeds the strength of deliberative cognitive control processes. The proposed experimental study seeks to improve understanding of the role of alcohol, implicit processes, and effortful control in risky sexual choice in men who have sex with men (MSM). We propose that alcohol intoxication increases the strength of relatively automatic approach biases toward sexual stimuli while simultaneously decreasing the role of more deliberative decision-making processes controlled by executive brain functions. This shift toward more implicit or automatic processes coupled with the decreased role of explicit decision- making processes increases the likelihood of sexual risk behavior and potentially limits the effectiveness of interventions that focus solely on explicit processes to promote behavioral change. The long-term aim of this research is explicating processes occurring in the heat of the moment when an individual's better judgment seems conspicuously absent and the drive for immediate gratification peaks. The proposed study will lay a foundation for innovative approaches to treatment that address both automatic and effortful processes to reduce sexual risk behavior in MSM.

? DESCRIPTION (provided by applicant): The societal impact of heavy alcohol consumption and chronic pain is substantial and warrants the existing research investment into their etiology and treatment. Moreover, evidence of significant co-occurrence between these conditions offers an opportunity to examine mechanisms in the alcohol-pain connection that may inform the development of novel treatments. Consistent with NIH PA-15-026 (Mechanistic Studies of Pain and Alcohol Dependence), the goal of the proposed study is to examine several complex and potentially bidirectional relations between pain and alcohol in one overarching model, which has never been attempted in a human experimental paradigm. The primary study aims are as follows: (1) to conduct the first test of both pharmacological and expectancy effects in acute alcohol analgesia among humans; (2) to conduct the first test of pain as a proximal antecedent of urge to drink and ad lib alcohol consumption, and to test whether acute analgesic effects predict pain-induced alcohol urge/consumption; (3) to test associations between study outcomes and candidate genetic polymorphisms that have been implicated in pain-alcohol processes; and (4) to conduct exploratory analyses of gender and pain relevant cognitive-affective factors as moderators of these outcomes. Participants will include 280 moderate-to-heavy drinkers recruited from the local community. Experimental methods will include alcohol administration (moderate dose vs. low dose vs. placebo vs. control) and pre/post assessment of static/dynamic pain responses (study visit 1), and capsaicin/heat pain induction (vs. no pain induction) followed by assessment of urge to drink and ad lib alcohol consumption (study visit 2). By employing a novel experimental paradigm, the study results will provide internally valid data with clear and direct implications for translating these findings to clinical applications. Itis our expectation that this work will catalyze future research and inform clinical practice by establishing an experimental platform that allows for the demonstration of causal effects, the evaluation of treatment components prior to conducting costly clinical trials, and the identification of important theory-based biopsychosocial mechanisms that can inform the development of novel integrated treatments for individuals with co-occurring pain and alcohol use disorders.

? DESCRIPTION (provided by the applicant): The NIH has been a global leader in supporting research toward the improvement of both behavioral and biomedical, as well as combined, HIV prevention and treatment interventions. Although there have been significant advances in both general HIV basic and intervention trials research, and in research on the acute effects of alcohol on HIV-­related sexual risk, a gap remains on the intersection of these two bodies of knowledge. NIAAA has long supported basic behavioral and social research as a foundation for HIV prevention interventions as part of its HIV/AIDS research portfolio. Recent examples of NIAAA's support of such research include its subscription to NIH FOAs PA-­13-­121, Research on alcohol and HIV/AIDS, and PA-­14-­061, Substance use and abuse, risky decision-­making, and HIV-­AIDS. Of direct relevance to the proposed application, since 2005 NIAAA has sponsored three (2005, 2007, and 2014, respectively) workshops held in the Washington, DC area dedicated to bringing together invited basic and prevention science alcohol/HIV/AIDS researchers to discuss their research and to foster communication and collaborations between the basic research and prevention science communities. The main objective of this application is to use the foundation laid through NIAAA's prior efforts by convening alcohol/HIV researchers in order to discuss and disseminate recent research findings toward the explicit end of integrating that knowledge into models of HIV prevention and thereby HIV behavioral primary and secondary interventions ultimately to enhance their effectiveness. The proposed series of four conference meetings/workshops, given their timing and context, will allow presentation of information to a wide array of alcohol/HIV researchers in a focused, timely manner that will accelerate the advance of behavioral HIV prevention interventions in a way that is not feasible given current limitations in the resources available to NIAAA programs to sponsor conferences and workshops.

Abstract Alcohol consumption at hazardous levels is associated with negative consequences on nearly every step of the HIV care continuum. It is a critical factor in HIV treatment that, if unaddressed, significantly contributes to onward transmission and poor treatment outcomes. Alcohol interventions for people living with HIV (PLWH) in the United States (US) have shown mixed results, and no alcohol intervention for PLHW has shown long-term reductions in heavy drinking or a significant impact on HIV-related outcomes. One hypothesized reason for this limited success is the failure of these interventions to address the multiple overlapping problems (e.g., co- morbid mental health conditions, behavioral health needs) of PLWH who are hazardous drinkers. Innovative alcohol intervention strategies that can have an impact on these multiple behavioral health needs, in a format that can be feasibly delivered in the context of HIV care, are needed. Brief Acceptance and Commitment Therapy (ACT) is a promising intervention for HIV-infected hazardous drinkers. ACT is a transdiagnostic treatment that uses mindfulness skills and values-guided behavioral action plans to impact a broad array of psychological symptoms. ACT has shown efficacy for treatment of anxiety, depression, chronic pain, and substance use, making it a promising approach for hazardous drinkers. The overall objective of this application is to adapt an existing brief ACT intervention developed for smoking cessation, and pilot test its feasibility and acceptability for PLWH who are hazardous drinkers. We hypothesize that the resulting intervention will be preliminarily associated with decreased alcohol use, improved ART adherence, decreased symptoms of depression, anxiety, and drug use, and increased acceptance?a known mechanism of change in ACT. The specific aims are as follows: Aim 1?we will adapt an existing brief ACT intervention for HIV-infected hazardous drinkers (ACT-AU). We will accomplish this aim by: Modifying a 5-session, telephone-delivered ACT intervention for smoking cessation via iterative multidisciplinary team meetings, focus group discussions with HIV clinic patients (N = 15-20), and qualitative interviews with HIV clinic providers (N = 5-10). Aim 2?we will conduct a pilot comparative effectiveness randomized clinical trial (RCT) of ACT-AU compared to a brief alcohol intervention previously shown to reduce drinking days among HIV-infected women. We will accomplish this aim by: Randomly assigning N = 74 HIV-infected hazardous drinkers (50% women) to the intervention developed in Aim 1, or a brief alcohol intervention similar in length and frequency of treatment sessions. We will assess feasibility, acceptability, and preliminary trial outcomes. Alcohol use and ART adherence will be assessed via both self-report and biomarkers at 6-weeks and 6-months post-randomization; preliminary changes in acceptance as well as symptoms of anxiety and depression, and drug use will also be examined 6- weeks and 3 and 6-months post-randomization. The proposed research will provide essential pilot data for a R01 application to conduct a full-scale RCT to determine the comparative efficacy of ACT-AU.  

Abstract The COVID-19 pandemic has had a significant impact on the mental health and alcohol use of the United States (US) general population, and has disproportionately affected people living with HIV (PLWH). Alcohol consumption and stress are both critical factors in HIV treatment that, if unaddressed, can significantly contribute to onward transmission and poor treatment-related outcomes. Alcohol interventions for PLWH in the US have shown mixed results. One hypothesized reason for this limited success is the failure of these interventions to address the multiple overlapping problems (e.g., co-morbid mental health conditions, stress, behavioral health needs) of PLWH who are hazardous drinkers. Innovative alcohol intervention strategies that can have an impact on these multiple behavioral health needs, in a format that can be feasibly delivered in the context of HIV care, are needed, especially in the context of the COVID-19 pandemic. Brief Acceptance and Commitment Therapy (ACT) is a promising intervention for HIV-infected hazardous drinkers. ACT is a transdiagnostic treatment that uses mindfulness skills and values-guided behavioral action plans to impact a broad array of psychological symptoms. ACT has shown efficacy for treatment of anxiety, depression, chronic pain, and substance use, and is thus a promising approach for PLWH who are hazardous drinkers and coping with additional stress related to the COVID-19 pandemic. We are proposing to expand our ongoing, NIAAA- funded (R34AA026246), pilot RCT of a telephone-delivered ACT intervention for PLWH by applying for an administrative supplement in response to the Notice of Special Interest on Stress Management in Relation to COVID-19 (NOT-AT-20-011). The overall objective of this application is to use the infrastructure of our ongoing pilot RCT (NCT0397406) to collect preliminary data on the level of stress experienced by PLWH during the COVID-19 pandemic, and to determine if participants in the RCT find the stress management techniques in our ACT intervention useful and applicable for the management of COVID-related stress. The specific aims are as follows: Aim 1: Incorporate objective and self-reported measures of stress into the pilot RCT. We will accomplish this aim by: adding general and pandemic-specific self-report measures of stress, and self- collected samples of salivary cortisol to all study visits, including a newly added 12-month follow-up. Aim 2: Determine the feasibility and acceptability of ACT as a telephone-based stress management intervention for PLWH during the COVID-19 pandemic. We will accomplish this aim by modifying our treatment manuals to incorporate COVID-19 related stress, and examining stress-related RCT outcomes by treatment condition. This administrative supplement will provide important information on COVID-related stress among PLWH, and provide data on the feasibility and potential efficacy of telephone-delivered ACT for stress management.