AIDS, Alcohol Dependence, Hazardous Drinking, Human Immunodeficiency Virus, Problem Drinking
Conditions
Keywords
HIV, Acquired Immunodeficiency Syndrome, Alcohol dependence, CD4, HIV-1 RNA, Alcohol treatment outcomes
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.
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.
Interventions
DRUGVivitrol- 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.
DRUGPlacebo
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.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Those Maintain or Improve to HIV RNA-1 Viral Load Less Then 400 Copies/mL | 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
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Treatment Outcome: Time to Alcohol Relapse | Post release | Self reported time to first heavy drinking day after release from incarceration, up to 6 months |
| Alcohol Treatment Outcome: Change in Average Drinks Per Drinking Day | 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 |
| Alcohol Treatment Outcome: Change in Percent of Heavy Drinking Days | 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
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in CD4 Cell Count (Cells/mL) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Extended-release 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.
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. | 67 |
| 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: 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. | 33 |
| Total | 100 |
Baseline characteristics
| Characteristic | Extended-release Naltrexone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 67 Participants | 33 Participants | 100 Participants |
| Age, Continuous | 44.9 years STANDARD_DEVIATION 8.1 | 45.2 years STANDARD_DEVIATION 8.9 | 45.0 years STANDARD_DEVIATION 8.4 |
| Alcohol use severity by AUDIT Abstinent or Low Risk Drinking | 2 participants | 0 participants | 2 participants |
| Alcohol use severity by AUDIT Harmful Drinking | 0 participants | 4 participants | 4 participants |
| Alcohol use severity by AUDIT Hazardous Drinking | 5 participants | 2 participants | 7 participants |
| Alcohol use severity by AUDIT Possible Dependence | 60 participants | 27 participants | 87 participants |
| Race/Ethnicity, Customized Black (non Hispanic) | 46 participants | 19 participants | 65 participants |
| Race/Ethnicity, Customized Hispanic | 11 participants | 8 participants | 19 participants |
| Race/Ethnicity, Customized White (non Hispanic) | 10 participants | 6 participants | 16 participants |
| Region of Enrollment United States | 67 participants | 33 participants | 100 participants |
| Sex: Female, Male Female | 16 Participants | 5 Participants | 21 Participants |
| Sex: Female, Male Male | 51 Participants | 28 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 67 | 2 / 33 |
| serious Total, serious adverse events | 0 / 67 | 0 / 33 |
Outcome results
Primary
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.
Time frame: Baseline to month 6 post release
Population: Logistic regression backward stepwise models were used to find predictors of HIV viral suppression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intramuscular Naltrexone | Percentage of Those Maintain or Improve to HIV RNA-1 Viral Load Less Then 400 Copies/mL | 54 percent of participants |
| Placebo | Percentage of Those Maintain or Improve to HIV RNA-1 Viral Load Less Then 400 Copies/mL | 42 percent of participants |
Secondary
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
Time frame: 12 weeks prior to release from prison (baseline) to 6 months post release
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intramuscular Naltrexone | Alcohol Treatment Outcome: Change in Average Drinks Per Drinking Day | -16.6 standard units of alcohol | Standard Deviation 22.2 |
| Placebo | Alcohol Treatment Outcome: Change in Average Drinks Per Drinking Day | -29.6 standard units of alcohol | Standard Deviation 27.5 |
| Extended-release Naltrexone, Received 4-6 Injections | Alcohol Treatment Outcome: Change in Average Drinks Per Drinking Day | -17.4 standard units of alcohol | Standard Deviation 25 |
| Placebo, Received 4-6 Injections | Alcohol Treatment Outcome: Change in Average Drinks Per Drinking Day | -14.9 standard units of alcohol | Standard Deviation 16.3 |
Secondary
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.
Time frame: change in percent of heavy drinking days12 weeks prior to release from prison (baseline), day of release, to 6 months post-release
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intramuscular Naltrexone | Alcohol Treatment Outcome: Change in Percent of Heavy Drinking Days | -38.3 percent of heavy drinking days | Standard Deviation 44.8 |
| Placebo | Alcohol Treatment Outcome: Change in Percent of Heavy Drinking Days | -51.3 percent of heavy drinking days | Standard Deviation 41.1 |
| Extended-release Naltrexone, Received 4-6 Injections | Alcohol Treatment Outcome: Change in Percent of Heavy Drinking Days | -63.6 percent of heavy drinking days | Standard Deviation 38.8 |
| Placebo, Received 4-6 Injections | Alcohol Treatment Outcome: Change in Percent of Heavy Drinking Days | -54.9 percent of heavy drinking days | Standard Deviation 46.9 |
Secondary
Alcohol Treatment Outcome: Time to Alcohol Relapse
Self reported time to first heavy drinking day after release from incarceration, up to 6 months
Time frame: Post release
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intramuscular Naltrexone | Alcohol Treatment Outcome: Time to Alcohol Relapse | Age 20-29 | 24.1 days | Standard Deviation 25.8 |
| Intramuscular Naltrexone | Alcohol Treatment Outcome: Time to Alcohol Relapse | Age 30-39 | 78.9 days | Standard Deviation 49.5 |
| Intramuscular Naltrexone | Alcohol Treatment Outcome: Time to Alcohol Relapse | Agge 40-49 | 98.8 days | Standard Deviation 70.4 |
| Intramuscular Naltrexone | Alcohol Treatment Outcome: Time to Alcohol Relapse | Age 50+ | 60.3 days | Standard Deviation 74.1 |
| Placebo | Alcohol Treatment Outcome: Time to Alcohol Relapse | Age 50+ | 64.1 days | Standard Deviation 66.4 |
| Placebo | Alcohol Treatment Outcome: Time to Alcohol Relapse | Age 20-29 | 9.5 days | Standard Deviation 10.6 |
| Placebo | Alcohol Treatment Outcome: Time to Alcohol Relapse | Agge 40-49 | 85.0 days | Standard Deviation 66.9 |
| Placebo | Alcohol Treatment Outcome: Time to Alcohol Relapse | Age 30-39 | 73.9 days | Standard Deviation 90.1 |
Other Pre-specified
Mean Change in CD4 Cell Count (Cells/mL)
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.
Time frame: Baseline and every 3 months for 1 year
Population: These data were not able to be collected for analysis.