Alcohol Pharmacotherapy for HIV+ Prisoners

Study Overview
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Brief Summary
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This is a randomized controlled trial of injectable intramuscular naltrexone (XR-NTX) versus intramuscular placebo among HIV-infected prisoners meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for alcohol dependence or problem drinking, who are transitioning to the community and seeking treatment to prevent relapse to alcohol use. We hypothesize that extended release naltrexone (XR-NTX) will result in improved HIV outcomes (lower log10 HIV-1RNA levels and higher CD4 count) as well as improved alcohol treatment outcomes, and reduced drug/sex HIV related risk behaviors and decreased rates of reincarceration.

Detailed Description
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INSPIRE is a randomized controlled trial of injectable intramuscular NTX (XR-NTX) versus intramuscular placebo among Human Immunodeficiency (HIV) infected prisoners meeting DSM-IV criteria for alcohol dependence or problem drinking, who are transitioning to the community and seeking treatment to prevent relapse to alcohol use. While the COMBINE trial has demonstrated the effectiveness of oral naltrexone in a group of active alcohol dependent persons in decreasing relapse to alcohol use over placebo, naltrexone has not been studied in people who have a history of current alcohol dependence prior to incarceration, are incarcerated and not actively using alcohol and are likely to return to alcohol use when released. In this study, we conduct a placebo-controlled trial to determine if naltrexone has an effect in this group, which could be important in making the case for having naltrexone available to alcohol dependent or problem drinking HIV+ prisoners prior to release. We will compare their HIV treatment (HIV-1 RNA levels, CD4 count), alcohol treatment (time to relapse to heavy drinking, percent of days drinking, percent of days abstinent and alcohol craving) and HIV risk behavior (sexual and drug-related risks) outcomes. The hypotheses include: i. XR-NTX will result in improved HIV clinical outcomes, including changes in HIV-1 RNA levels, and higher CD4 counts. ii. XR-NTX will result in improved alcohol treatment outcomes, including longer time to alcohol relapse, lower percent days drinking, and lower craving for alcohol.

Official Title
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Alcohol Pharmacotherapy for HIV+ Prisoners With Alcohol Dependence and Problem Drinking

Conditions
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Alcohol Dependence, Problem Drinking, Hazardous Drinking, Human Immunodeficiency Virus, AIDS

Intervention / Treatment
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* Drug: Vivitrol- Intramuscular naltrexone (depot-formulation)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV+ Inmates returning to New Haven or Hartford Meets criteria for alcohol dependence (using Diagnostic and Statistical Manual IV) or problem drinking (using Alcohol Use Disorder Identification Test-AUDIT) Gives informed consent English or Spanish speaker > 18 yrs Exclusion Criteria: On opiate pain medication or expressing need for them Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) > 5x the upper limit of normal Evidence of Child's Pugh Class C cirrhosis Pending felony charges Pregnant or unwilling to take contraceptive measures Subject is part of another pharmacological research study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intramuscular naltrexone<br>Subjects in this arm will receive monthly intramuscular gluteal injections of depot naltrexone 380mg (VIVITROL) for 6 months. The 1st injection will be administered prior to release from prison or jail. | Drug: Vivitrol- Intramuscular naltrexone (depot-formulation)<br>* Subjects in this arm will receive monthly intramuscular gluteal injections of depot naltrexone 380mg (VIVITROL) for 6 months. The 1st injection will be administered prior to release from prison or jail.<br>* Other names: Depot-naltrexone;|
| Placebo Comparator: Placebo<br>Subjects in this arm will receive monthly intramuscular gluteal injections of placebo for 6 months. The 1st injection will be administered prior to release from prison or jail. | Drug: Placebo<br>* Subjects in this arm will receive monthly intramuscular gluteal injections of placebo for 6 months. The 1st injection will be administered prior to release from prison or jail. Placebo will be provided by Alkermes pharmaceuticals, the manufacturer of VIVITROL. Placebo will be identical in shape and form to active drug.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Those Maintain or Improve to HIV RNA-1 Viral Load Less Then 400 Copies/mL | Percentage of participants that maintained or improved a level of undetectable HIV viral load from baseline (closest viral load to time of release from incarceration) to 6 months post release. Missing lab values were considered to have a detectable HIV viral load. | Baseline to month 6 post release | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Treatment Outcome: Time to Alcohol Relapse | Self reported time to first heavy drinking day after release from incarceration, up to 6 months | Post release | 
| Alcohol Treatment Outcome: Change in Average Drinks Per Drinking Day | The mean change from 12 weeks pre incarceration to 6 months post release from incarceration in average drinks per drinking day | 12 weeks prior to release from prison (baseline) to 6 months post release | 
| Alcohol Treatment Outcome: Change in Percent of Heavy Drinking Days | change in the percent of heavy drinking days from 12 weeks prior to incarceration to 6 months post release from incarceration. | change in percent of heavy drinking days12 weeks prior to release from prison (baseline), day of release, to 6 months post-release | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD4, HIV, Acquired Immunodeficiency Syndrome, Alcohol dependence, HIV-1 RNA, Alcohol treatment outcomes