Combined Motivational Interviewing and Ecological Momentary Intervention to Reduce Hazardous Alcohol Use Among Sexual Minority Cisgender Men and Transgender Individuals: Protocol for a Randomized Controlled Trial

Background Sexual minority cisgender men and transgender (SMMT) individuals, particularly emerging adults (aged 18-34 years), often report hazardous drinking. Given that alcohol use increases the likelihood of HIV risk behaviors, and HIV disproportionately affects SMMT individuals, there is a need to test interventions that reduce hazardous alcohol use and subsequent HIV risk behaviors among this population. Ecological momentary interventions (EMIs), which use mobile phones to deliver risk reduction messages based on current location and behaviors, can help to address triggers that lead to drinking in real time. Objective This study will test an EMI that uses motivational interviewing (MI), smartphone surveys, mobile breathalyzers, and location tracking to provide real-time messaging that addresses triggers for drinking when SMMT individuals visit locations associated with hazardous alcohol use. In addition, the intervention will deliver harm reduction messaging if individuals report engaging in alcohol use. Methods We will conduct a 3-arm randomized controlled trial (N=405 HIV-negative SMMT individuals; n=135, 33% per arm) comparing the following conditions: (1) Tracking and Reducing Alcohol Consumption (a smartphone-delivered 4-session MI intervention), (2) Tracking and Reducing Alcohol Consumption and Environmental Risk (an EMI combining MI with real-time messaging based on geographic locations that are triggers to drinking), and (3) a smartphone-based alcohol monitoring–only control group. Breathalyzer results and daily self-reports will be used to assess the primary and secondary outcomes of drinking days, drinks per drinking day, binge drinking episodes, and HIV risk behaviors. Additional assessments at baseline, 3 months, 6 months, and 9 months will evaluate exploratory long-term outcomes. Results The study is part of a 5-year research project funded in August 2022 by the National Institute on Alcohol Abuse and Alcoholism. The first 1.5 years of the study will be dedicated to planning and development activities, including formative research, app design and testing, and message design and testing. The subsequent 3.5 years will see the study complete participant recruitment, data collection, analyses, report writing, and dissemination. We expect to complete all study data collection in or before January 2027. Conclusions This study will provide novel evidence about the relative efficacy of using a smartphone-delivered MI intervention and real-time messaging to address triggers for hazardous alcohol use and sexual risk behaviors. The EMI approach, which incorporates location-based preventive messaging and behavior surveys, may help to better understand the complexity of daily stressors among SMMT individuals and their impact on hazardous alcohol use and HIV risk behaviors. The tailoring of this intervention toward SMMT individuals helps to address their underrepresentation in existing alcohol use research and will be promising for informing where structural alcohol use prevention and treatment interventions are needed to support SMMT individuals. Trial Registration ClinicalTrials.gov NCT05576350; https://www.clinicaltrials.gov/study/NCT05576350 International Registered Report Identifier (IRRID) PRR1-10.2196/55166

1 R01 AA030487-01 3 ZAA1 DD (17) LAUCKNER, C cisgender and heterosexual.This is concerning, as alcohol use contributes to HIV risk and HIV disproportionately affects this population.Through a randomized controlled trial, the proposed research will evaluate an enhanced motivational interviewing intervention that utilizes smartphones and mobile breathalyzers to provide real-time messaging that addresses triggers for drinking when individuals visit locations associated with risky alcohol use.

CRITIQUE 1
Significance: 3 Investigator(s): 3 Innovation: 2 Approach: 6 Environment: 1 Overall Impact: This proposal aims to conduct a 3-arm randomized controlled trial that assesses the efficacy of two interventions relative to control in reducing alcohol use and HIV-related sexual risk behavior among sexual minority men and transgender people.The two active interventions are: 1) an 8-week motivational interviewing intervention (TRAC) delivered remotely, and 2) TRAC combined with an ecological momentary intervention that will deliver drinking reduction text messages when individuals visit risky locations (GeoTRAC).The control condition will be EMA completion only (i.e., daily surveys and twice daily mobile breathalyzer).Breathalyzer results and daily self-reports will be used to assess the primary and secondary outcomes of drinking days, drinks per drinking day, binge drinking episodes, and HIV risk behaviors at 8 weeks, 6 months, and 12 months post-intervention.The proposal is seen as significant, the investigative team is strong, and there are some interesting points of innovation (e.g., geographically triggered risk reduction messaging).However, there are also a number of issues that dampen my enthusiasm.Major concerns include the grouping together of sexual minority men and transgender people throughout the proposal (without consideration of these groups' unique needs), lack of clarity in the description of the risk reduction text messages, and issues related to recruitment.

Strengths
• Sexual minority male and transgender emerging adults have high rates of hazardous drinking and alcohol use disorders, and this is particularly pronounced among emerging adults.
• These groups are also disproportionately impacted by HIV.
• Alcohol use is linked to various indicators of risk for HIV, so reducing alcohol use may also reduce risk for HIV infection.
• Motivational Interviewing is an effective strategy for reducing alcohol use and HIV-related risk behaviors among MSM.

Weaknesses
• Much of the data presented to support this study are from samples of sexual minority males, and there are times when these data are used as citations to support statements about specific health behaviors/risks of transgender people.Overall, more attention is needed to the unique/common experiences of transgender people in order to effectively include them in the study.

Investigator(s):
Strengths • PI Lauckner is strong early career investigator with an impressive portfolio of funded research and existing collaborations with the other MPI.
• PI Kershaw has extensive experience in HIV and alcohol use among MSM.
• This proposal has a strong biostatistician.
• Co-I Fallin-Bennet has nice complementary experience working with SGM patients in healthcare settings.
• The presence of an endocrinologist who works with transgender patients is an asset.

Weaknesses
• While the team has experience with transgender people in a clinical context, there is no apparent expertise in research with transgender people, particularly research on alcohol use and HIV.
• The MPI plan doesn't say much about how the PIs roles differ, except that each will run operations at their own site.I'd like to see more detail about the differing areas of expertise and/or different roles each PI will play.

Strengths
• The ability to provide risk reduction messages in the moment when participants enter venues they've previously designated as "risky" is novel and could have high impact.
• The use of a mobile breathalyzer to get an objective measure of alcohol use is innovative.

Weaknesses
• None noted

Strengths
• The team presents strong preliminary data on TRAC with convincing interim analyses.
• The inclusion of risk reduction messages that are triggered by geographical factors is strong.
• The 3-arm RCT is well-described and robust.

Weaknesses
• One of my biggest concerns is the grouping together of sexual minority men and transgender people throughout the proposal and study design.Transgender people have unique experiences that likely influence their drinking and sexual behavior.Will these be addressed?If so, how?It is also not evident whether the team has experience recruiting transgender people into research from these clinical settings.
• The investigators present a conceptual model for their intervention that includes numerous antecedents (e.g., stress, stigma), but it is not clear as to how/if these antecedents are integrated into the intervention.
• I have some concerns about the recruitment plan.Based on the recruitment strategy, there will be major differences between sites in the proportion of transgender people and sexual minority men.And there will also be major differences between sites in the specific recruitment strategies being used.Thus, it will not be clear if observed differences are due to gender identity, recruitment method, or state/region.
• Another major issue is that there will not be an inclusion criterion for HIV risk.There is high variability between individuals in HIV risk, even among drinkers.Thus, secondary analyses on HIV risk behavior will likely be underpowered.Further, it won't be clear if participants are even having sex with men at the time of enrollment (e.g., bisexual individuals, transgender people who don't have sex with men), and these people will be at very low risk for HIV.
• There is some lack of clarity in the content of the text messages.How are the messages being generated?How is the team selecting what messages to send at different locations?How will the team handle situations like drinking at home (will participants get a notification every time they walk in their door)?Will the messages be tailored to the unique experiences of transgender people and sexual minority men, or will they be the same messages?
• The HIV-related outcomes lack precision, and there are no descriptions of the HIV-related analyses.For example, sex without a condom may not always be problematic (e.g., if the participant is in a seroconcordant monogamous relationship, the participant is on PrEP).
• How might incentivized participant referral influence the integrity of the RCT?

Strengths
• The infrastructures at University of Kentucky and Yale are very strong and will support the proposed project.
• The Center for Health Equity Transformation and the CTSA at Kentucky are strong additional support.
• The Center for Interdisciplinary Research on AIDS at Yale is a strong environment for this research.

Strengths
• The timeline is detailed and appropriate.

Protections for Human Subjects:
Acceptable Risks and/or Adequate Protections
• For NIH-Defined Phase III trials, Plans for valid design and analysis: Not applicable.
• Inclusion/Exclusion Based on Age: Distribution justified scientifically.
• Distribution justified scientifically across factors.

Resource Sharing Plans:
• Acceptable

Budget and Period of Support:
• Recommend as Requested

CRITIQUE 2
Significance: 2 Investigator(s): 1 Innovation: 1 Approach: 4 Environment: 1 Overall Impact: This project aims to conduct a trial to evaluate motivational interviewing with smartphone-based alcohol monitoring (TRAC/SAM) as compared to an enhanced version of TRAC/SAM that uses an ecological momentary intervention to trigger alcohol messages based on physical location.The hypothesis is that the enhanced intervention will lead to a larger reduction in number of drinking days than TRAC/SAM or SAM alone by offering more precise messaging and support.The team is excellent, the research design is rigorous, the concept is innovative, and the proposal builds on an excellent set of preliminary data.There are some concerns about how geofencing will work, software development plans and whether this is feasible in six months, and the potential for response fatigue with twice daily breathalyzers/surveys and how this will be accounted for.

Strengths
• SGM experience high rates of hazardous drinking, which in turn increases the risk for HIV.
• Motivational interviewing could benefit SGM who drink especially if combined with an ecological momentary intervention.

Weaknesses
• The lack of evidence on MI approaches for SGM may warrant a more preliminary study before full-scale efficacy trial.Also questions are raised about whether MI is effective at changing shorter term outcomes, somewhat throwing into question the TRAC intervention which is based on MI.

Strengths
• MPI Lauckner is a productive early-stage researcher with sufficient experience in developing and testing interventions using MI with breathalyzers.MPI Kershaw is a senior researcher and adds complementary leadership around EMI interventions targeting alcohol use.
• Dr. Fallin-Bennet adds clinical expertise in this study population; Dr. Boyd will facilitate MI trainings; Dr. Hansen also has experience in the study population and in brief alcohol interventions.

Weaknesses
• None noted

Strengths
• Employing EMI using activity space assessment to reduce alcohol use is novel.
• The intervention will be fully-remote with potential for future scale-up, if efficacious, and has the potential to reduce disparities in access to alcohol services in this vulnerable population.

Weaknesses
• Smartphone apps to reduce alcohol use are not necessarily novel.

Strengths
• The combination of Lauckner's research on TRAC and Kershaw's work on the activity space assessments may be synergistic.The prior work suggests both components are very promising and may have a larger impact when combined.
• Activity space assessments to identify risky locations and trigger alcohol messages may offer more personalized alcohol support by responding in the moment.
• MI training of facilitators and fidelity assessment plans are rigorous.It appears that facilitators may also receive their MITI certificate prior to the start.This is a plus.

Weaknesses
• The study could benefit from a stronger theoretical grounded in how components involving MI, monitoring, and location-based messaging will lead to the anticipated behavior changes.
• While the study population has access to smartphones, their technical literacy is not well described, and it is not clear how support for technical difficulties will be provided for less technically-advanced participants.
• Unclear if prior work also offered incentivizes for completing breathalyzers and daily surveys.
This would offer support for the proposed strategy.
• A more major concern is the extent of the software development for the app, which often takes significantly longer than expected (only 6 months are budgeted).It is not clear what the app currently does and what will be added or modified for the proposed study.These plans should be more detailed to demonstrate feasibility.
• The list of "risky places" will be pre-determined qualitatively and then compared against GPS location, however, it is not clear how messages will be handled for people who mostly drink at home or at a friend's house.This could lead to fatigue, non-response, and reduced impact on behavior if messages are sent frequently.
• More detail could be provided on how participant GPS location will be compared against coordinates of risky locations and the range of error (is this off-the-shelf software or will this functionality be developed?).
• It is not clear how assessments will be administered (e.g., phone/online/CASI) and whether this approach has been successful in the past.
• Incentives will be used to maximize breathalyzer and survey responses, however, with 420 tasks per participant, response fatigue may still affect response rates and quality of data provided.There are no data to suggest what responses rates may be with this approach or plans to control for these issues in the analysis.

Strengths
• Resources and infrastructure at University of Kentucky, Yale, and Ohio State University are excellent.

Weaknesses
• Only six months are planned for software development to update the app, which seems very short.

Protections for Human Subjects:
Acceptable Risks and/or Adequate Protections Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): • Acceptable Inclusion Plans: • Sex/Gender: Distribution justified scientifically.
• For NIH-Defined Phase III trials, Plans for valid design and analysis: Not applicable.
• Inclusion/Exclusion Based on Age: Distribution justified scientifically.Overall Impact: The proposed study focuses on a critical population: emerging adult sexual minority male and transgender individuals are disproportionately burdened by hazardous drinking and alcohol use disorders, which is concerning as alcohol use contributes to HIV risk and HIV disproportionately affects this population.The investigators propose a randomized controlled trial to evaluate an enhanced motivational interviewing intervention that utilizes smartphones and mobile breathalyzers to provide real-time messaging that addresses triggers for drinking when individuals visit locations associated with risky alcohol use.Overall, the reviewer expresses strong enthusiasm for this project, with some minor, addressable, concerns, mainly related to the lack of discussion about implementation science or focus on understanding further scale up or dissemination of the intervention approaches being evaluated.It is also not clear how the investigators will assess and account for treatment-seeking among participants.

Strengths
• The target population of the proposed study, sexual minority male and transgender emerging adults frequently engage in hazardous drinking and have high rates of alcohol use disorders, which contributes to risk of HIV transmission.
• Ecological momentary interventions, when paired with an MI intervention, could provide realtime support in addressing triggers for drinking while also reinforcing content discussed during MI sessions.

Weaknesses
• No mention of implementation science or focus on understanding further scale up or dissemination of the intervention approaches being evaluated.

Strengths
• study team has experience in conducting MI interventions, working with SMMT populations in research and clinical settings, and using smartphones to collect substance use data.
• The planned research builds on ongoing grant-funded studies led by the investigators and represents an innovative step forward in their programs of research and in the literature regarding alcohol use interventions for SMMT individuals.• Not clear evidence of previous or ongoing collaborations among the study team, especially in the proposed study locations.

Strengths
• Assesses and addresses the role of geographic context.
• Objectively assess alcohol use with breathalyzer technology.

Weaknesses
• None noted

Strengths
• Proposed study builds off of promising preliminary studies being conducted by the investigative team.

• it is essential to test interventions for reducing alcohol use among SMMT individuals as a means
of preventing HIV among this vulnerable population.
• Technology can be used to extend the impact of MI by delivering messaging to prevent risk behaviors in real time.

Weaknesses
• No mention of implementation science or focus on understanding further scale up or dissemination of the intervention approaches being evaluated.
• It is unclear how investigators will address who do not want to (1) reduce their drinking and/or (2) participate in the intervention (e.g., prefer different treatment approaches, among those randomized into different intervention arms)?

Strengths
• All investigators' institutions are strong with adequate resources to successfully carry out the proposed project.

Strengths
• Appropriate study timeline.
• For NIH-Defined Phase III trials, Plans for valid design and analysis: Scientifically acceptable.
• Inclusion/Exclusion Based on Age: Distribution justified scientifically.

Budget and Period of Support:
Recommended budget modifications or possible overlap identified: • Acceptable

THE FOLLOWING SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE, OR REVIEWERS' WRITTEN CRITIQUES, ON THE FOLLOWING ISSUES: PROTECTION OF HUMAN SUBJECTS: ACCEPTABLE INCLUSION OF WOMEN PLAN: ACCEPTABLE INCLUSION OF MINORITIES PLAN: ACCEPTABLE INCLUSION ACROSS THE LIFESPAN: ACCEPTABLE COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested.
Footnotes for 1 R01 AA030487-01; PI Name: Lauckner, Carolyn NIH has modified its policy regarding the receipt of resubmissions (amended applications).See Guide Notice NOT-OD-18-197 at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-197.html.The impact/priority score is calculated after discussion of an application by averaging the overall scores (1-9) given by all voting reviewers on the committee and multiplying by 10.The criterion scores are submitted prior to the meeting by the individual reviewers assigned to an application, and are not discussed specifically at the review meeting or calculated into the overall impact score.Some applications also receive a percentile ranking.For details on the review process, see http://grants.nih.gov/grants/peer_review_process.htm#scoring.

Response to Reviews: Application # 1R01AA030487-01 (mPIs: Lauckner & Kershaw)
Our application had the benefit of a rigorous and favorable scientific peer review.We are pleased that the committee was highly enthusiastic about the innovation of the proposal, and that they felt the investigative team was strong with complementary expertise.This letter serves to further strengthen the application by responding positively to the few minor weaknesses raised by reviewers that did not damper the fact that the committee's overall enthusiasm for the application project remained high.Below are the main comments from reviewers and how we will modify our proposal to address these comments.
Justification for the inclusion of both sexual minority men (SMM) and transgender (trans) individuals, and discussion of how the unique experiences of trans people will be integrated in the study design.
Although there is considerably less research on trans individuals compared to SMM on alcohol use and HIV, the research available has shown: 1) high rates of alcohol use problems and alcohol use disorders for trans compared to cisgender populations, 1,2 and 2) the link between increased HIV risk behavior and both overall alcohol use and event-level alcohol use for trans individuals. 1,3Further, the few motivational interviewing (MI) interventions that have been conducted with trans individuals have shown effectiveness on alcohol and substance use reduction, demonstrating promise for MI as a tool to reduce alcohol use among trans individuals. 4This suggests that trans individuals are an ideal population for an alcohol and HIV risk reduction intervention using MI.
Further, reviewers wanted justification for combining SMM and trans individuals in the intervention given the differences between these populations.We will address the unique experiences and needs of SMM and trans individuals by: (a) using MI as the primary intervention component for both TRAC and GeoTRAC, a therapeutic technique that has been used successfully for both SMM and trans individuals 4 and which allows us to tailor intervention components based on the experiences, triggers, and context of the individual.Because MI uses an individualized approach, we will be able to deliver an intervention that is specific to the needs of SMM and trans individuals; (b) developing the place-based messaging used in GeoTRAC using triggers identified through MI sessions, which further facilitates tailored messaging and accounts for the specific experiences and needs of both SMM and trans individuals; (c) utilizing separate focus groups conducted with SMM and trans individuals (2 SMM and 2 trans sessions) to develop the harm-reduction messages (which are sent to GeoTRAC participants who test positive for alcohol using the breathalyzer), which will allow us to select messages that resonate the most for each subgroup; and (d) assessing for possible moderating effects by sexual and gender identity groups to determine if there are differential effects of the intervention by subgroup.
Finally, reviewers felt the team would be strengthened by adding a behavioral researcher with expertise in HIV and alcohol use among trans individuals to complement our strong clinical expertise in trans health.In response, we added Dr. Arjee Restar to our study team as a co-Investigator.6][7][8] She will provide expertise in HIV and substance use among trans individuals and provide consultation on study and intervention design, recruitment techniques of trans individuals, and measurement and assessment.

More clarification on recruitment strategies and inclusion criteria.
Reviewers wanted clarification on how we would address differences in population characteristics (number of SMM/trans people) and recruitment strategies between the two sites.To address potential site effects, randomization will be stratified by site and SMM/trans subgroup, reducing the likelihood of confounding across conditions.
Reviewers also felt that because we did not include HIV risk level as inclusion criteria that we may be underpowered to detect differences on our secondary HIV-risk outcomes.To address this, we will include the CDC's PrEP eligibility criteria (as an indicator of HIV risk) as inclusion criteria.Individuals will be eligible if they have had anal or vaginal sex in the past 6 months and have at least one of the following characteristics: a sexual partner with HIV; inconsistent condom/PrEP use; or a sexually transmitted disease diagnosis in the past 6 months.This addition to our criteria will ensure participants have both high levels of alcohol and HIV risk.

More information on the feasibility of app development and testing
Reviewers were concerned about the feasibility of modifying our current app as needed for this study in the proposed 6 month timeline.The proposed app shares most of the same functionality as the apps used in our current RENEW and MVMNT studies (R01HD092185 and R01AA025954).Table 1 shows the overlapping functionality of the RENEW/MVMNT apps and GeoTRAC, with new functions bolded.The majority of the app functions are shared between RENEW/ MVMNT apps and GeoTRAC, suggesting modifications for GeoTRAC will be more a refinement of functionalities than widespread development of new functions.Further, we recently modified the current app for an F31 to create an EMI intervention that delivers place-based messages (very similar to what we are proposing for GeoTRAC) for individuals in substance use treatment, and a beta version was created in <1 month.Given the overlap in functionality between the RENEW/ MVMNT apps and the proposed GeoTRAC app, as well as our recent track record for a similar modification of the apps for EMI delivery, a 6-month time frame is realistic.
Reviewers also wanted more information on the range of error of GPS location and geofencing technology.We developed the functionality for using geofencing to trigger assessments and messages for our RENEW/MVMNT apps and have tested it extensively for our 2 R01s, including Beta testing and concurrent monitoring of accuracy for our study participants (i.e., we ask participants at each interview if there were times when they went to locations where they did not receive assessments).We have conducted over 1300 placebased triggered surveys and have received only a small number of reported inaccuracies (<15) in locationbased triggered assessments.
Reviewers also wanted clarification on how messaging for the GeoTRAC arm would handle locations that are highly-frequented (e.g., homes) to avoid message overload.For these locations (determined by the initial activity space assessment), we will collect information about specific times when triggers/drinking behavior are highest and will only send messages when they are at those high-frequency locations at those specific times (e.g., at home after 5pm on weekends).Also, to reduce message burden, we will cap messages for a specific location at 2/day and no more often than every 2 hours.Reviewers were also concerned about possible fatigue related to completing twice-daily breathalyzer and survey responses.In our previous studies, with similar frequencies of breathalyzers and surveys over 8 weeks with comparable incentives, we saw high rates of completion (70% of breathalyzers in TRAC; daily survey completion rates >75%), suggesting that we have a track record of conducting these assessments with minimum fatigue.

More information on how we will handle variations in technological expertise and literacy.
We have considerable experience working with populations with varied levels of technological literacy and have developed strong procedures to provide training on the use and navigation of both smartphones and the specific technologic components of our study (e.g., apps, breathalyzer).Participants in each condition will be trained to navigate the app including completing assessments, opening messages, completing breathalyzer readings, and implementing data safety and confidentiality procedures.Wallet sized cards with information from the training will be provided.We will also do regular checks at assessments and MI sessions to allow participants to report problems, and we will complete video calls to troubleshoot if needed.Finally, the app will include functionality for participants to contact the study team if they experience technical difficulties.

More clarity on the description of the content of the risk reduction text messages.
Reviewers wanted more clarity on how intervention message content will be developed.One of the innovations of the current study is that intervention messaging delivered by the GeoTRAC app will be tailored to each individual based on responses from their MI sessions and activity space assessments.Participants will identify which type of triggers they experience at their locations during the activity space assessments and then develop strategies for addressing these triggers during their MI sessions.These strategies will be entered in the back-end of the app for each individual, allowing for tailored messaging when they go to those locations.The messages will generally utilize the following formula: "Looks like you '

re at [INSERT LOCATION NAME HERE]. Because sometimes you experience [TYPE OF TRIGGER] here, don't forget that you can [INSERT STRATEGY HERE] if you feel an urge to drink."
Messages will continue to be added as individuals progress through TRAC, incorporating different triggers and strategies identified through their work in the MI sessions.

More information on the unique expertise of the MPIs and previous collaborations of the study team.
Drs. Lauckner and Kershaw bring shared but unique expertise to the proposed project that provides a strong team science model.Dr. Lauckner is an expert on mHealth and telehealth, MI interventions, and

•
Risks are minimal and protections acceptable.

Table 1 :
Functions of Current Apps and Proposed GeoTRAC App RENEW/MVMNT Apps Proposed GeoTRAC App Tracks GPS Tracks GPS Creates geofence around places to trigger action from the app Creates geofence around places to trigger action from the app Sends daily and place-based surveys and messages Sends daily and place-based surveys and messages Provides reminders for appointments, missed surveys Provides reminders for appointments, missed surveys Allows participants to contact study team Allows participants to contact study team Incorporates