Alcohol Pharmacotherapy for HIV+ Prisoners (INSPIRE)

• ClinicalTrials.gov Identifier: NCT01077310
• Recruitment Status: Completed
• First Posted: March 1, 2010
• Results First Posted: November 25, 2016
• Last Update Posted: May 30, 2017
• Sponsor: Yale University
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Alcohol Dependence; Problem Drinking; Hazardous Drinking; Human Immunodeficiency Virus; AIDS	Drug: Vivitrol- Intramuscular naltrexone (depot-formulation); Drug: Placebo	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Alcohol Pharmacotherapy for HIV+ Prisoners With Alcohol Dependence and Problem Drinking
• Study Start Date: August 2010
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Intramuscular naltrexone; 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); 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.; Other Names: VIVITROL; extended release naltrexone; Intramuscular naltrexone; Depot-naltrexone
Placebo Comparator: Placebo; 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; 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.; Other Name: Saline

Outcome Measures

Primary Outcome Measures :

1. Percentage of Those Maintain or Improve to HIV RNA-1 Viral Load Less Then 400 Copies/mL [ Time Frame: Baseline to month 6 post release ]
   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.

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Mean Change in CD4 Cell Count (Cells/mL) [ Time Frame: Baseline and every 3 months for 1 year ]
   Baseline labs will be drawn while subjects is in prison, one to three months prior to release. Additionally, blood will be drawn every 3 months for 1 year to monitor changes in CD4 cell count.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. HIV+
2. Inmates returning to New Haven or Hartford
3. Meets criteria for alcohol dependence (using Diagnostic and Statistical Manual IV) or problem drinking (using Alcohol Use Disorder Identification Test-AUDIT)
4. Gives informed consent
5. English or Spanish speaker
6. > 18 yrs

Exclusion Criteria:

1. On opiate pain medication or expressing need for them
2. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) > 5x the upper limit of normal
3. Evidence of Child's Pugh Class C cirrhosis
4. Pending felony charges
5. Pregnant or unwilling to take contraceptive measures
6. Subject is part of another pharmacological research study

Contacts and Locations

Locations

United States, Connecticut

Yale Clinical Research

New Haven, Connecticut, United States, 06511

Sponsors and Collaborators

Yale University

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Sandra A Springer, MD; Yale University
• Principal Investigator: Frederick L Altice, MD; Yale University

More Information

Publications of Results:

Vagenas P, Di Paola A, Herme M, Lincoln T, Skiest DJ, Altice FL, Springer SA. An evaluation of hepatic enzyme elevations among HIV-infected released prisoners enrolled in two randomized placebo-controlled trials of extended release naltrexone. J Subst Abuse Treat. 2014 Jul;47(1):35-40. doi: 10.1016/j.jsat.2014.02.008. Epub 2014 Mar 12. Erratum in: J Subst Abuse Treat. 2017 Jun;77:44.

Springer SA, Brown SE, Di Paola A, Altice FL. Correlates of retention on extended-release naltrexone among persons living with HIV infection transitioning to the community from the criminal justice system. Drug Alcohol Depend. 2015 Dec 1;157:158-65. doi: 10.1016/j.drugalcdep.2015.10.023. Epub 2015 Oct 28. Erratum in: Drug Alcohol Depend. ;161:372. Altice, Frederick L [added].

Other Publications:

Springer SA, Altice FL, Herme M, Di Paola A. Design and methods of a double blind randomized placebo-controlled trial of extended-release naltrexone for alcohol dependent and hazardous drinking prisoners with HIV who are transitioning to the community. Contemp Clin Trials. 2014 Mar;37(2):209-18. doi: 10.1016/j.cct.2013.12.006. Epub 2013 Dec 31. Erratum in: Contemp Clin Trials. 2017 Jun;57:98.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Springer SA, Di Paola A, Barbour R, Azar MM, Altice FL. Extended-release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living with HIV and Alcohol use Disorders Transitioning to the Community: Results From a Double-Blind, Placebo-Controlled Trial. J Acquir Immune Defic Syndr. 2018 Sep 1;79(1):92-100. doi: 10.1097/QAI.0000000000001759.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01077310
• Other Study ID Numbers: 0908005572; 1R01AA018944 ( U.S. NIH Grant/Contract )
• First Posted: March 1, 2010
• Results First Posted: November 25, 2016
• Last Update Posted: May 30, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Yale University:

HIV; Acquired Immunodeficiency Syndrome; Alcohol dependence; CD4; HIV-1 RNA; Alcohol treatment outcomes

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Alcoholism; Immune System Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Slow Virus Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Naltrexone; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents