Comparing Treatments for HIV-Infected Opioid and Alcohol Users in an Integrated Care Effectiveness Study

Study Overview
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Brief Summary
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The purpose of this study is to learn how best to treat substance use disorders in an HIV clinic setting. Specifically, the purpose of this pilot study is to learn if extended-release naltrexone (XR-NTX) would be a feasible and acceptable treatment for HIV-infected individuals with opioid or alcohol use disorders.

Official Title
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Comparing Treatments for HIV-Infected Opioid and Alcohol Users in an Integrated Care Effectiveness Study

Conditions
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Opioid Use Disorder, Alcohol Use Disorder

Intervention / Treatment
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* Drug: Extended Release Naltrexone
* Other: Treatment As usual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet Diagnostic and Statistical Manual (DSM-5) criteria for moderate or severe opioid use disorder and/or alcohol use disorder. Be willing to be randomized to antagonist-based therapy or treatment as usual (TAU) for treatment of opioid and/or alcohol use disorders. Be HIV-infected as defined by history of positive HIV serology or HIV RNA pcr >10,000 copies/mL). Be willing to establish ongoing HIV care at community treatment program(CTP) if not already receiving ongoing care. Be willing to initiate antiretroviral therapy (ART) if not already prescribed ART, regardless of CD4 count. Be at least 18 years old. Be able to provide written informed consent and HIPAA (if applicable) for medical record abstraction. Be able to communicate in English. If female, be willing to take measures to avoid becoming pregnant. Exclusion Criteria: Individuals will be excluded from pilot study participation if they: Have a serious medical, psychiatric or substance use disorder that, in the opinion of the study physician, would make study participation hazardous to the participant, compromise study findings, or prevent the participant from completing the study. Examples include: Disabling or terminal medical illness (e.g., active opportunistic infection, uncompensated heart failure, cirrhosis or end-stage liver disease, acute hepatitis and moderate to severe renal impairment) as assessed by medical history, review of systems, physical exam and/or laboratory assessments; Severe, untreated or inadequately treated mental health disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview; Current severe benzodiazepine or other depressant or sedative hypnotic use requiring medical detoxification; Suicidal or homicidal ideation requiring immediate attention. Have aspartate aminotransferase (AST) or alanine aminotransferase (ALT) liver enzymes greater than 5 times upper limit of normal on screening phlebotomy. Results from tests conducted within the past 30 days which are abstracted from medical record information are acceptable. Have international normalized ratio (INR) > 1.5 or platelet count <100k. Results from tests conducted within the past 30 days which are abstracted from medical record information are acceptable. Have known allergy or sensitivity to naloxone, naltrexone, polylactide-co-glycolide, carboxymethylcellulose, or other components of the Vivitrol® diluents. Anticipate undergoing surgery during study participation. Have chronic pain requiring ongoing pain management with opioid analgesics. Pending legal action or other reasons that might prevent an individual from completing the study. Currently pregnant or breastfeeding. Body habitus that, in the judgment of the study physician, precludes safe intramuscular injection of XR-NTX, (e.g. excess fat tissue over the buttocks). Received methadone or buprenorphine maintenance therapy for treatment of opioid dependence in the 4 weeks prior to screening. Have taken an investigational drug in another study within 30 days of study consent. Have ECG findings that, in the opinion of the study medical clinician would preclude safe participation in the study. Results from ECGs conducted within the past 30 days which are abstracted from medical record information are acceptable. Have had treatment with XR-NTX for opioid or alcohol dependence in the 3 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment as Usual<br>The current standard of care for treatment of opioid use disorders in HIV clinics is opioid agonist therapy. HIV-infected patients with alcohol use disorders are typically referred for residential, outpatient, and self-help groups. | Other: Treatment As usual<br> <br> |
| Experimental: Extended Release Naltrexone<br>Extended release naltrexone (XR-NTX), delivered by monthly injection. Dose: 380 mg. Frequency: One injection per month, for four months. Duration: 30 days. | Drug: Extended Release Naltrexone<br> <br> * Other names: Vivitrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Successful Initiation of Treatment Within 4 Weeks of Randomization | Successful induction onto XR-NTX or initiation of treatment as usual within 4 weeks of randomization. | 4 weeks | 
| Number of Participants Successfully Retained on Pharmacotherapy Treatment at 16 Weeks | Number of participants who received the maximum possible expected doses of XR-NTX, or the full course of recommended pharmacotherapy treatment for treatment as usual (TAU) arm. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV Viral Suppression at 16 Weeks | Plasma HIV viral load of < 200 copies/mL compared with screening | 16 weeks | 
| Mean Days of Opioid Use in Past 30 Days | Change in 30 day opioid use by Addiction Severity Index (ASI)-lite self-report and Time-Line Follow Back in the final 30 days of the 16 week trial compared to screening. | Baseline and 16 weeks | 
| HIV Care Engagement | Change in the proportion of participants prescribed antiretroviral therapy (ART) within 16 weeks following randomization, compared to baseline. | Baseline and 16 weeks | 
| Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Change in liver enzymes between screening and Week 16. AST = Aspartate transaminase ALT = Alanine transaminase | Baseline and 16 weeks | 
| Number of Participants With Urine Drug Screen (UDS) Positive for Opioids |  | Baseline and 16 weeks | 
| Mean Days of Alcohol Use in Past 30 Days | Change in 30 day alcohol use by Addiction Severity Index (ASI)-lite self-report and Time-Line Follow Back in the final 30 days of the 16 week trial compared to screening. | Baseline and 16 weeks | 
| Number of Participants With Urine Ethyl Glucuronide (EtG) Positive for Alcohol |  | Baseline and 16 weeks | 
| Participant Safety: Any Fatal or Non-fatal Overdose Between Baseline and Week 16 |  | 16 weeks | 
| Participant Safety: Precipitated Withdrawal | Proportion of participants assigned to XR-NTX who develop precipitated opioid withdrawal. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Substance related disorders, HIV, naltrexone