Binge Drinking, HIV
Conditions
Keywords
Naltrexone
Brief summary
This is a double-blind, placebo-controlled trial of 120 binge-drinking MSM to 12 weeks of naltrexone 50mg, to be taken in anticipation of heavy drinking. Ethnically and racially diverse participants will be recruited using Respondent Driven Sampling as well as active field recruitment. MSM will be seen weekly for alcohol-metabolite urine testing, study drug dispensing, and brief counseling for alcohol use. Safety assessments and behavioral surveys will be completed monthly.
Detailed description
This is a double-blinded, placebo controlled trial of 120 binge-drinking MSM to 12 weeks of naltrexone 50mg, to be taken in anticipation of heavy drinking. Ethically and racially diverse participants will be recruited using venue based recruitment and social network bsed recruitment strategies. Participants will be seen weekly for alcohol metabolite urine testing, study drug dispensing and brief counseling for alcohol use. Safety assessments and behavioral surveys will be completed monthly. Efficacy on alcohol consumption and alcohol-associated sexual risk behavior (Aims 1-3) will be assessed using weekly timeline follow-back, screening for ethyl glucuronide (EtG) positive urines, and computer administered monthly interventions. Tolerability and acceptability (Aim 4) will be assessed through tracking of adverse events and medication adherence. Generalized estimating equation (GEE) models will be fitted to estimate treatment effects on repeated study outcomes.
Interventions
DRUGPlacebo
Placebo capsules will contain microcrystalline cellulose (Medisca). Placebo and active medication will be provided in capsules that are an exact match in color, so as to make the placebo and active medication indistinguishable from each other.
DRUGNaltrexone
REVIA is a white, crystalline compound. The hydrochloride salt is soluble in water to the extent of about 100 mg/mL. REVIA is available in scored film-coated tablets containing 50 mg of naltrexone hydrochloride.
MM is a low-intensity supportive program designed to increase problem recognition and enhance motivation to change maladaptive alcohol use patterns. Participants will receive individual 20 minute MM sessions weekly from trained staff supervised by a clinical psychologist
DIAGNOSTIC_TESTUrinalysis for novel alcohol biochemical markers:
Urine samples will be collected weekly and tested for ethyl glucuronide (EtG) to determine recent alcohol consumption. EtG is a relatively novel, highly sensitive indicator for recent alcohol consumption; this alcohol biomarker is detectable in urine for approximately 72 hours).
BEHAVIORALBehavioral survey measurements:
Standardized and validated behavioral measure that will be assessed using audio computer administered surveys (ACASI) to minimize underreporting of risk activities and standardize data collection
DIAGNOSTIC_TESTDried Blood Spot (DSB) Testing for Phosphatidylethanol
Phosphatidylethanol (PEth)-a phospholipid formed only in the presence of alcohol-is a novel, direct biochemical marker of alcohol that has shown high (\>95%) sensitivity and specificity to detect heavy drinking over a period of 2-3 weeks in several studies of dependent patients and abstainers. DSB samples will be collected at enrollment, weeks 3, 6, 9, 12, and post-treatment visits at month 1, 3, and 6.
BEHAVIORALEcological Momentary Assessment
Ecological Momentary Assessments are SMS texts to collect data on alcohol consumption, number of drinks on drinking days, and targeted medication administration prior to anticipated drinking sessions. Messages will use short-hand notations to maintain participant confidentiality
Sponsors
San Francisco Department of Public Health
National Institutes of Health (NIH)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* (1) Male gender (2) self-reported anal sex with men in the prior three months while under the influence of alcohol (3) at least one binge drinking (five or more drinks on a single occasion) session per week in the prior three months; (4) interested in reducing binge alcohol consumption; (5) HIV-negative by rapid antibody test or medical record documentation of HIV infection (HIV positive participants); (6) no current acute illnesses requiring prolonged medical care; (7) no chronic illnesses that are likely to progress clinically during trial participation; (8) able and willing to provide informed consent and adhere to visit schedule; (9) age 18-70 years; (10) baseline complete blood count (CBC), total protein, albumin, glucose, alkaline phosphatase, creatinine, blood urea nitrogen (BUN), and electrolytes without clinically significant abnormalities as determined by study clinician in conjunction with symptoms, physical exam, and medical history.
Exclusion criteria
* (1) Any psychiatric (e.g. depression with suicidal ideation) or medical condition that would preclude safe participation in the study; (2) known allergy/previous adverse reaction to naltrexone; (3) current use of/ dependence on any opioids or a known medical condition which currently requires/may likely require opioid analgesics; (4) opioid-positive urine at enrollment; (5) current CD4 count \< 200 cells/mm3 (6) moderate/severe liver disease (aspartate aminotransferase (AST), alanine transaminase (ALT) \> 3 times upper limit of normal); (7) impaired renal function (creatinine clearance \< 50 ml/min); (8) currently participating in another intervention research study with potential overlap; (9) alcohol dependence as determined by Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID) criteria (participants with non-dependent alcohol use disorders/symptoms of alcohol abuse (per Diagnostic and Statistical Manual--DSM-IV) are eligible) (10) any condition that, in the principal investigator and/or study clinician's judgment interferes with safe study participation or adherence to study procedures; (11) not having a cell-phone that can send and receive text messages.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Binge Drinking Days Per Week | 12 weeks | This outcome measure determines the mean number of binge drinking days among participants randomized to targeted naltrexone and placebo arms. The Center for Disease Control (CDC) defines binge drinking as consuming 5 or more drinks on an occasion for men or 4 or more drinks on an occasion for women. |
| Positive Ethyl Glucuronide (EtG) Tests | 12 weeks | This outcome measure determines the number of participants with positive ethyl glucuronide tests among non-dependent MSM who were randomized to targeted naltrexone and placebo arms. Ethyl glucuronide (EtG) is a non-volatile, water-soluble, stable, direct metabolite of ethanol that can be detected in urine for 48 hours or sometimes 72 hours after drinking if there is heavy drinking. |
| Male Anal Sex Partners | 12 weeks | This outcome measure determines the mean number of male anal sex partners among non-dependent MSM randomized to targeted naltrexone and placebo arms. |
| Unprotected Anal Sex Partners While Intoxicated With Alcohol | 12 weeks | This outcome measure determines the mean number of unprotected anal sex partners while intoxicated with alcohol among targeted naltrexone and placebo arms . |
| HIV-serodiscordant Unprotected Anal Sex Partners | 12 weeks | This outcome measure determines the mean number of HIV-serodiscordant unprotected anal sex partners among the targeted naltrexone and placebo arms. |
| Unprotected Anal Sex Events With Serodiscordant Partners | 12 weeks | This outcome measure determines the mean number of unprotected anal sex events with serodiscordant partners |
Countries
United States
Participant flow
Recruitment details
Participants were recruited via street outreach, recruitment flyers, sexual health clinics, needle exchanges, community organizations, bars, websites, and social media in San Francisco Bay Area.
Pre-assignment details
Potential participants completed a brief telephone screen to assess initial eligibility and, if eligible, were scheduled for an in-person screening visit. All participants gave informed consent using University of California, San Francisco (UCSF) IRB-approved consent forms. Participants were evaluated for eligibility based on the inclusion criteria during the in-person screening visit.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo 50mg, as needed
Placebo | 60 |
| Naltrexone Naltrexone 50mg, as needed
Naltrexone | 60 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 7 |
Baseline characteristics
| Characteristic | Placebo | Naltrexone | Total |
|---|---|---|---|
| Age, Continuous | 34 years | 38 years | 37 years |
| Alcohol Craving Scale-Visual Analog | 25 units on a scale | 30 units on a scale | 30 units on a scale |
| Alcohol Use Disorder Identification Test (AUDIT) | 17 units on a scale | 16 units on a scale | 17 units on a scale |
| Center for Epidemiological Studies Depression scale (CES-D) | 13 units on a scale | 12 units on a scale | 12 units on a scale |
| Education college or above | 35 Participants | 36 Participants | 71 Participants |
| Education high school or less | 6 Participants | 7 Participants | 13 Participants |
| Education some college | 19 Participants | 17 Participants | 36 Participants |
| Employment employed student | 5 Participants | 2 Participants | 7 Participants |
| Employment full-time | 29 Participants | 28 Participants | 57 Participants |
| Employment not employed | 14 Participants | 21 Participants | 35 Participants |
| Employment part-time | 12 Participants | 9 Participants | 21 Participants |
| Ever hospitalized for alcohol problem No | 54 Participants | 50 Participants | 104 Participants |
| Ever hospitalized for alcohol problem Yes | 6 Participants | 10 Participants | 16 Participants |
| Ever received alcohol treatment Missing | 9 Participants | 7 Participants | 16 Participants |
| Ever received alcohol treatment No | 43 Participants | 42 Participants | 85 Participants |
| Ever received alcohol treatment Yes | 8 Participants | 11 Participants | 19 Participants |
| Has health insurance No | 6 Participants | 5 Participants | 11 Participants |
| Has health insurance Yes | 54 Participants | 55 Participants | 109 Participants |
| Has regular health care provider No | 10 Participants | 8 Participants | 18 Participants |
| Has regular health care provider Yes | 50 Participants | 52 Participants | 102 Participants |
| HIV Status HIV-negative | 43 Participants | 46 Participants | 89 Participants |
| HIV Status HIV-positive | 17 Participants | 14 Participants | 31 Participants |
| Income $20 - 39,999 | 17 Participants | 12 Participants | 29 Participants |
| Income $40,000 and above | 30 Participants | 32 Participants | 62 Participants |
| Income under $20,000 | 13 Participants | 16 Participants | 29 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 12 Participants | 17 Participants |
| Race/Ethnicity, Customized Latino | 10 Participants | 2 Participants | 12 Participants |
| Race/Ethnicity, Customized Other | 9 Participants | 11 Participants | 20 Participants |
| Race/Ethnicity, Customized White | 32 Participants | 33 Participants | 65 Participants |
| Region of Enrollment United States | 60 Participants | 60 Participants | 120 Participants |
| Sex/Gender, Customized Gender Identity Cis-gender male | 59 Participants | 60 Participants | 119 Participants |
| Sex/Gender, Customized Gender Identity Transgender male (female to male) | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 60 |
| other Total, other adverse events | 20 / 60 | 43 / 60 |
| serious Total, serious adverse events | 1 / 60 | 1 / 60 |
Outcome results
Primary
Binge Drinking Days Per Week
This outcome measure determines the mean number of binge drinking days among participants randomized to targeted naltrexone and placebo arms. The Center for Disease Control (CDC) defines binge drinking as consuming 5 or more drinks on an occasion for men or 4 or more drinks on an occasion for women.
Time frame: 12 weeks
Population: The binge drinking days analysis between targeted naltrexone and placebo arms is different from the participant flow chart. The overall number of participants is calculated from those participants that completed the ACASI survey at week 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Targeted Naltrexone/Placebo | Binge Drinking Days Per Week | Naltrexone Arm | 1.056 days per week | Standard Deviation 1.522 |
| Targeted Naltrexone/Placebo | Binge Drinking Days Per Week | Placebo Arm | 1.722 days per week | Standard Deviation 1.698 |
Primary
HIV-serodiscordant Unprotected Anal Sex Partners
This outcome measure determines the mean number of HIV-serodiscordant unprotected anal sex partners among the targeted naltrexone and placebo arms.
Time frame: 12 weeks
Population: The overall number of participant analyzed for HIV-serodiscordant unprotected anal sex partners is based on the participants who completed the week 12 survey. This is different than the participant flow.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Targeted Naltrexone/Placebo | HIV-serodiscordant Unprotected Anal Sex Partners | Targeted Naltrexone | 0.28 partners | Standard Deviation 0.45 |
| Targeted Naltrexone/Placebo | HIV-serodiscordant Unprotected Anal Sex Partners | Placebo | 0.26 partners | Standard Deviation 0.44 |
Primary
Male Anal Sex Partners
This outcome measure determines the mean number of male anal sex partners among non-dependent MSM randomized to targeted naltrexone and placebo arms.
Time frame: 12 weeks
Population: The overall number of participants analyzed for Male anal sex partners is based on those who completed the week 12 ACASI survey. This is different than the participant flow. There were 54 participants in each arm of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Targeted Naltrexone/Placebo | Male Anal Sex Partners | Targeted Naltrexone | 1.06 sex partners | Standard Deviation 1.41 |
| Targeted Naltrexone/Placebo | Male Anal Sex Partners | Placebo | 1.98 sex partners | Standard Deviation 3.59 |
Primary
Positive Ethyl Glucuronide (EtG) Tests
This outcome measure determines the number of participants with positive ethyl glucuronide tests among non-dependent MSM who were randomized to targeted naltrexone and placebo arms. Ethyl glucuronide (EtG) is a non-volatile, water-soluble, stable, direct metabolite of ethanol that can be detected in urine for 48 hours or sometimes 72 hours after drinking if there is heavy drinking.
Time frame: 12 weeks
Population: A total of 50 participants were analyzed in the targeted naltrexone arm and 52 participants were analyzed in the placebo arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Targeted Naltrexone/Placebo | Positive Ethyl Glucuronide (EtG) Tests | Targeted Naltrexone | 23 Participants |
| Targeted Naltrexone/Placebo | Positive Ethyl Glucuronide (EtG) Tests | Placebo | 29 Participants |
Primary
Unprotected Anal Sex Events With Serodiscordant Partners
This outcome measure determines the mean number of unprotected anal sex events with serodiscordant partners
Time frame: 12 weeks
Population: The overall number of participants analyzed is based on those who completed the week 12 survey. This is different than the participant flow. There are 54 participants in each arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Targeted Naltrexone/Placebo | Unprotected Anal Sex Events With Serodiscordant Partners | Placebo | 0.41 events | Standard Deviation 0.92 |
| Targeted Naltrexone/Placebo | Unprotected Anal Sex Events With Serodiscordant Partners | Targeted Naltrexone | 0.81 events | Standard Deviation 2 |
Primary
Unprotected Anal Sex Partners While Intoxicated With Alcohol
This outcome measure determines the mean number of unprotected anal sex partners while intoxicated with alcohol among targeted naltrexone and placebo arms .
Time frame: 12 weeks
Population: The overall number of participants analyzed for Unprotected anal sex partners while intoxicated with alcohol is based on the number of participants who completed the week 12 survey. This is different than the participant flow. There were 54 participants in the targeted naltrexone and the placebo arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Targeted Naltrexone/Placebo | Unprotected Anal Sex Partners While Intoxicated With Alcohol | Targeted Naltrexone | 0.96 partners | Standard Deviation 1.52 |
| Targeted Naltrexone/Placebo | Unprotected Anal Sex Partners While Intoxicated With Alcohol | Placebo | 0.56 partners | Standard Deviation 0.95 |