Intermittent Naltrexone Among Polysubstance Users

Study Overview
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Brief Summary
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Naltrexone, a µ-opioid receptor antagonist, is a promising agent for methamphetamine-using and binge-drinking men who have sex with men (MSM). Naltrexone has shown efficacy in reducing relapse to amphetamines and is FDA-approved for alcohol dependence. Oral naltrexone is inexpensive and has few toxicities but the standard daily regimen for naltrexone is problematic as patients forget to take the medication. Given the challenges in daily dosing, alternate regimen schedules have been proposed to increase efficacy and expand the population that may benefit from this pharmacologic agent. One approach is intermittent targeted administration of naltrexone, whereby individuals take the medication as-needed in anticipation of substance use or during periods of craving. Administration of naltrexone prior to exposure to amphetamines significantly attenuates craving and targeted naltrexone has shown efficacy in reducing heavy alcohol use. However, there have been no studies assessing intermittent targeted dosing of naltrexone among methamphetamine-using and binge-drinking MSM. Polysubstance use patterns are common among MSM, and studies among those who abuse more than one substance are urgently needed. The aims of this study are to determine whether targeted dosing of naltrexone is feasible, tolerable and acceptable among non-dependent methamphetamine-using and binge-drinking MSM.

Conditions
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Methamphetamine, Alcohol

Intervention / Treatment
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* Drug: Intermittent Oral Naltrexone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male gender or transgender male-to-female self-reported anal sex with men in the prior six months while under the influence of meth and/or alcohol self-reported meth use at least bi-weekly in the prior three months at least weekly binge drinking (five or more drinks on a single drinking session) in the prior three months 4) interested in reducing meth use and/or binge drinking 5) HIV-negative by rapid test or medical record of HIV infection 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: any psychiatric (e.g., depression with suicidal ideation) or medical condition that would preclude safe participation in the protocol known allergy or previous adverse reaction to naltrexone current use of or dependence on any opioids or a known medical condition which currently requires or may likely require opioid analgesics opioid-positive urine test at enrollment current cluster of differentiation 4 (CD4) count < 200 cells/mm3 moderate or severe liver disease (aspartate aminotransferase, alanine aminotransferase, or total bilirubin > 3 times upper limit of normal) impaired renal function (creatinine clearance < 60 ml/min) currently participating in another research study meth or alcohol dependence as determined by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) criteria any condition that, in the principal investigator and/or study clinician's judgment interferes with safe participation or adherence to study procedures. unwillingness to provide minimum locator for information not having a cellular phone that can send or receive a text message plans to leave the Bay Area during study follow-up not comfortable speaking and reading English, enough to participate in a program in English

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Naltrexone<br>Intermittent oral naltrexone to be taken on an as-needed basis for 8 weeks. | Drug: Intermittent Oral Naltrexone<br> <br> |
| Placebo Comparator: Placebo<br>Intermittent oral placebo to be taken on an as-needed basis for 8 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Retaining Participants in Trial | Proportion of persons retained by study arm. | proportions eligible and enrolled assessed on ongoing basis throughout the study, proportion of visits completed assessed bi-weekly for each participant; overall retention assessed over 2 month follow-up for each participant | 
| Acceptability to Taking Medication | Mean number of pills taken weekly, as determined by recorded openings from an electronic monitoring device for study medication pill dispensers | 2 month follow-up | 
| Tolerability to Study Drug, as Measured by Adverse Events | Frequency of Adverse Events, by arm | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol, HIV, sexual behavior, methamphetamine