Naltrexone for Opioid Dependent Released Human Immunodeficiency Virus Positive (HIV+) Criminal Justice Populations

Study Overview
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Brief Summary
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Specific Aim: To conduct a randomized, placebo-controlled trial of extended release-naltrexone (XR-NTX) among Human Immunodeficiency Virus (HIV) infected prisoners meeting Diagnostic Statistical Manual IV (DSM-IV) criteria for opioid dependence who are transitioning from the structure of a correctional setting to the community. Hypotheses: i. XR-NTX will result in improved HIV clinical outcomes, including lower changes in HIV-1 RNA levels, higher CD4 counts and higher rates of retention in care. ii. XR-NTX will result in improved opioid treatment outcomes, including longer time to opioid relapse, lower addiction severity and lower craving for opioid. iii. XR-NTX will result in reduced drug- and sex-related HIV risk behaviors compared to the control group. iv. XR-NTX will result in decreased rates of reincarceration after 12 months of release to the community.

Detailed Description
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The specific aim for this study is to conduct a placebo-controlled trail (RCT) of XR-NTX among HIV+ persons in jails and prisons meeting DSM-IV criteria for opioid dependence who are transitioning to the community. HIV treatment outcomes (HIV-1 RNA levels, CD4 count, Highly Active Antiretroviral Therapy (HAART) adherence, retention in care), substance abuse (time to relapse to opioid use, % opioid negative urines, opioid craving), adverse side effects and HIV risk behavior (sexual and drug-related risks) outcomes will be compared in 150 recruited prisoners and jail detainees in Connecticut (CT) and Massachusetts (MA) who will be randomized 2:1 to either XR-NTX or placebo. The primary outcome of interest will be the proportion with a HIV-RNA <400 copies/mL at 6 months. Secondary outcomes include mean CD4 count, antiretroviral adherence, retention on HAART and in HIV care, HIV risk behaviors, time-to-relapse to opioid use, percent opioid negative urines, retention on d-NTX and HIV quality of life. Primary and secondary outcomes will be assessed for an additional 6 months after completion of the intervention. If this placebo-controlled trial of XR-NTX among released HIV+ criminal justice system (CJS) persons with opioid dependence demonstrates efficacy and safety, it is likely to become an evidence-based intervention to intervene with this extremely marginalized population in a way that will meet Healthy People 2010's goals to increase the quality and years of life, decrease health disparities particularly among minorities, break the cycle of addiction, reduce the numbers of people within the CJS and launch a number of new and innovative trials and second generation questions for future research. As such, the individual, our health care system and society have a high likelihood to benefit. This will not only be true for strategies here in the U.S., but may have even greater application for geographic areas where the interface between opioid disorders and HIV is even greater.

Official Title
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Naltrexone for Opioid Dependent Released Human Immunodeficiency Virus Positive (HIV+) Criminal Justice Populations

Conditions
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HIV, AIDS, Opioid Dependence, Drug Dependence

Intervention / Treatment
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* Drug: Extended-Release Naltrexone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets DSM-IV criteria for opioid dependence Age > 18 years Confirmed HIV infection, either through positive HIV antibody or detectable HIV-1 RNA level. Within the Connecticut Department of Corrections (CTDOC) or Hampden County Correctional Center (HCCC) and within 30 days of being released to the greater New Haven, Hartford or Springfield areas or within 30 days after release from CTDOC or HCCC. No participation in pharmacotherapy trial in the previous 30 days Not pregnant Exclusion Criteria: Unable to provide informed consent Verbally or physically threatening to research staff Unable to communicate in either English or Spanish Pending trials for a felony Liver failure (Childs-Pugh Class B or C Cirrhosis) Grade IV Hepatitis (liver function tests > 10X normal) Receiving opioid prescription narcotics or has pain syndrome necessitating future use of opioid prescription narcotics. Receiving active methadone or buprenorphine/naloxone for the treatment of opioid dependency Active opioid withdrawal (within 3-5 days since last opioid ingestion) Pregnancy or unwilling to take contraceptives measures Breast-feeding

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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Accepts Healthy Volunteers

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: Extended-Release Naltrexone<br>Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release | Drug: Extended-Release Naltrexone<br>* Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg<br>* Other names: Vivitrol;|
| Placebo Comparator: Placebo<br>Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release | Drug: Extended-Release Naltrexone<br>* Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg<br>* Other names: Vivitrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Who Had Undetectable HIV-1 RNA Levels at Less Than 400 Copies/mL at Six Month | Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additionally, labs will be drawn every 3 months for 1 year to monitor changes in HIV-1 RNA levels. Treatment time period was the first 6 months where the primary outcome data will be based on. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Particpants Who Had Undetectable HIV-1 RNA Levels at Less Than 50 Copies/mL | Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additionally, labs will be drawn every 3 months for 1 year to monitor changes in HIV-1 RNA levels. Treatment time period was the first 6 months where the primary outcome data will be based on. | 6 months | 
| CD4 Cell Count (Cells/mL) | Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additional labs will be drawn every 3 months for 1 year to monitor changes in CD4 levels. | Baseline and 6 months | 
| Time to Opioid Relapse or End of Intervention | Measuring days to first relapse based on self reported opioids (heroin) use within the 6 month (180 days) intervention period. If participants had no follow-up visits, and thus no self reported opiate use, they were treated as missing. Those who did not relapse within the 6 month intervention period were treated as having 180 days until relapse. | 6 months | 
| Addiction Severity | The Addiction Severity Index (ASI) questionnaire will be used to assess addiction severity. The ASI composite scoreprovides reliable and valid measure of patient status in a particular module of interest which can then be usecompared at the beginning of treatment to the evaluation endpoint to note the improvement or lack thereof. In this assessment the drug composite score was calculated using algorithm by Treatment Research Institute. If the score increases then it shows increase in severity where as if it decreases then it shows decrease in severity for that measured module. The scale ranges from 0 to 1. The mean composite scores for drug use from baseline to 6 months were compared using Nonparametric test. | baseline, and 6 months | 
| Craving for Opioids | Craving at baseline compared to 6 month. This is assessed through a self report scale rated 0 to 10; 0 meaning not craving and 10 meaning highest craving. Change in craving score was categorized as 1)no change between baseline and 6 month; 2)increased craving - baseline craving was reported lower than at 6 month; 3)decreased craving - baseline craving was reported higher than 6 month craving. | 6 months | 
| Antiretroviral Therapy (ART) Adherence 100% | Number of subjects with 100% adherence at 6 months measured using Visual Analogue Scale: 0% to 100% | 6 months | 
| Participants With Opiate Abstinence Via By Doing Urine Toxicology Test | Percent of subjects with no opiate use at 6 month. Missing data was treated as failure (opiate positive). | 6 month | 
| Opioid Abstinence at 6 Months for Those With More Than 4 Injections | Based on self reported opioids (heroin) use. All participants receiving Placebo as well as participants who received 3 or less XR-NTX injections were compared to those who receive 4 or more XR-NTX injection. | 6 months | 
| ART Adherence for 4 or More Injections XR-NTX Versus Placebo and 3 or Less Injections of XR-NTX | The arm/group number of the participants vary from the primary outcome because this is a treatment effect analysis. All client with missing data at 6 months were considered as failure - meaning - they had less than 100% ART adherence. | 6 months |