Opioid Use Disorder, Alcohol Use Disorder
Conditions
Keywords
Substance related disorders, HIV, naltrexone
Brief summary
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.
Interventions
OTHERTreatment As usual
Sponsors
National Institute on Drug Abuse (NIDA)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Meet Diagnostic and Statistical Manual (DSM-5) criteria for moderate or severe opioid use disorder and/or alcohol use disorder. 2. Be willing to be randomized to antagonist-based therapy or treatment as usual (TAU) for treatment of opioid and/or alcohol use disorders. 3. Be HIV-infected as defined by history of positive HIV serology or HIV RNA pcr \>10,000 copies/mL). 4. Be willing to establish ongoing HIV care at community treatment program(CTP) if not already receiving ongoing care. 5. Be willing to initiate antiretroviral therapy (ART) if not already prescribed ART, regardless of CD4 count. 6. Be at least 18 years old. 7. Be able to provide written informed consent and HIPAA (if applicable) for medical record abstraction. 8. Be able to communicate in English. 9. 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: 1. 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; 1. Severe, untreated or inadequately treated mental health disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview; 2. Current severe benzodiazepine or other depressant or sedative hypnotic use requiring medical detoxification; 3. Suicidal or homicidal ideation requiring immediate attention. 2. 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. 3. 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. 4. Have known allergy or sensitivity to naloxone, naltrexone, polylactide-co-glycolide, carboxymethylcellulose, or other components of the Vivitrol® diluents. 5. Anticipate undergoing surgery during study participation. 6. Have chronic pain requiring ongoing pain management with opioid analgesics. 7. Pending legal action or other reasons that might prevent an individual from completing the study. 8. Currently pregnant or breastfeeding. 9. 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). 10. Received methadone or buprenorphine maintenance therapy for treatment of opioid dependence in the 4 weeks prior to screening. 11. Have taken an investigational drug in another study within 30 days of study consent. 12. 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. 13. Have had treatment with XR-NTX for opioid or alcohol dependence in the 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Successful Initiation of Treatment Within 4 Weeks of Randomization | 4 weeks | Successful induction onto XR-NTX or initiation of treatment as usual within 4 weeks of randomization. |
| Number of Participants Successfully Retained on Pharmacotherapy Treatment at 16 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HIV Care Engagement | Baseline and 16 weeks | Change in the proportion of participants prescribed antiretroviral therapy (ART) within 16 weeks following randomization, compared to baseline. |
| Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Baseline and 16 weeks | Change in liver enzymes between screening and Week 16. AST = Aspartate transaminase ALT = Alanine transaminase |
| Number of Participants With Urine Drug Screen (UDS) Positive for Opioids | Baseline and 16 weeks | — |
| HIV Viral Suppression at 16 Weeks | 16 weeks | Plasma HIV viral load of \< 200 copies/mL compared with screening |
| 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 | 16 weeks | Proportion of participants assigned to XR-NTX who develop precipitated opioid withdrawal. |
| Mean Days of Alcohol Use in Past 30 Days | Baseline and 16 weeks | 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. |
| Mean Days of Opioid Use in Past 30 Days | Baseline and 16 weeks | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment as Usual 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.
Treatment As usual | 26 |
| Extended Release Naltrexone Extended release naltrexone (XR-NTX), delivered by monthly injection. Dose: 380 mg. Frequency: One injection per month, for four months. Duration: 30 days.
Extended Release Naltrexone | 25 |
| Total | 51 |
Baseline characteristics
| Characteristic | Extended Release Naltrexone | Total | Treatment as Usual |
|---|---|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 8.8 | 46 years STANDARD_DEVIATION 10 | 45 years STANDARD_DEVIATION 12 |
| Region of Enrollment Canada | 12 Participants | 24 Participants | 12 Participants |
| Region of Enrollment United States | 13 Participants | 27 Participants | 14 Participants |
| Sex: Female, Male Female | 14 Participants | 22 Participants | 8 Participants |
| Sex: Female, Male Male | 11 Participants | 29 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 26 | 9 / 25 |
| serious Total, serious adverse events | 1 / 26 | 1 / 25 |
Outcome results
Primary
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.
Time frame: 16 weeks
Population: 24 TAU participants, and 17 XR-NTX participants initiated treatment in their respective arms. Treatment retention is calculated only for subjects who have been initiated onto treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment as Usual | Number of Participants Successfully Retained on Pharmacotherapy Treatment at 16 Weeks | 12 Participants |
| Extended Release Naltrexone | Number of Participants Successfully Retained on Pharmacotherapy Treatment at 16 Weeks | 15 Participants |
Primary
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.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment as Usual | Number of Participants With Successful Initiation of Treatment Within 4 Weeks of Randomization | 25 Participants |
| Extended Release Naltrexone | Number of Participants With Successful Initiation of Treatment Within 4 Weeks of Randomization | 17 Participants |
Secondary
HIV Care Engagement
Change in the proportion of participants prescribed antiretroviral therapy (ART) within 16 weeks following randomization, compared to baseline.
Time frame: Baseline and 16 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment as Usual | HIV Care Engagement | Prescribed ART at baseline | 25 Participants |
| Treatment as Usual | HIV Care Engagement | Prescribed ART at 16 weeks | 26 Participants |
| Extended Release Naltrexone | HIV Care Engagement | Prescribed ART at baseline | 23 Participants |
| Extended Release Naltrexone | HIV Care Engagement | Prescribed ART at 16 weeks | 24 Participants |
Secondary
HIV Viral Suppression at 16 Weeks
Plasma HIV viral load of \< 200 copies/mL compared with screening
Time frame: 16 weeks
Population: 23 TAU participants and 21 XR-NTX participants had a 16-week lab draw for HIV viral load testing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment as Usual | HIV Viral Suppression at 16 Weeks | 20 Participants |
| Extended Release Naltrexone | HIV Viral Suppression at 16 Weeks | 17 Participants |
Secondary
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.
Time frame: Baseline and 16 weeks
Population: In both the TAU and XR-NTX groups, reporting results for participants who were retained at 16 weeks and completed necessary study assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment as Usual | Mean Days of Alcohol Use in Past 30 Days | Baseline mean days alcohol use in past 30 days | 15.6 days | Standard Deviation 9.95 |
| Treatment as Usual | Mean Days of Alcohol Use in Past 30 Days | 16 weeks mean days alcohol use in past 30 days | 5.7 days | Standard Deviation 8.4 |
| Extended Release Naltrexone | Mean Days of Alcohol Use in Past 30 Days | Baseline mean days alcohol use in past 30 days | 12.5 days | Standard Deviation 11.02 |
| Extended Release Naltrexone | Mean Days of Alcohol Use in Past 30 Days | 16 weeks mean days alcohol use in past 30 days | 2.8 days | Standard Deviation 3.05 |
Secondary
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.
Time frame: Baseline and 16 weeks
Population: In both the TAU and XR-NTX groups, reporting results for participants who were retained at 16 weeks and completed necessary study assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment as Usual | Mean Days of Opioid Use in Past 30 Days | Baseline mean days opioid use in past 30 days | 17.3 days | Standard Deviation 13.14 |
| Treatment as Usual | Mean Days of Opioid Use in Past 30 Days | 16 weeks mean days opioid use in past 30 days | 4.1 days | Standard Deviation 5.43 |
| Extended Release Naltrexone | Mean Days of Opioid Use in Past 30 Days | Baseline mean days opioid use in past 30 days | 20.3 days | Standard Deviation 12.29 |
| Extended Release Naltrexone | Mean Days of Opioid Use in Past 30 Days | 16 weeks mean days opioid use in past 30 days | 7.7 days | Standard Deviation 11.32 |
Secondary
Number of Participants With Urine Drug Screen (UDS) Positive for Opioids
Time frame: Baseline and 16 weeks
Population: In both the TAU and XR-NTX groups, reporting results for participants who were retained at 16 weeks and completed necessary study assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment as Usual | Number of Participants With Urine Drug Screen (UDS) Positive for Opioids | Baseline UDS positive for opioids | 9 Participants |
| Treatment as Usual | Number of Participants With Urine Drug Screen (UDS) Positive for Opioids | 16 weeks UDS positive for opioids | 7 Participants |
| Extended Release Naltrexone | Number of Participants With Urine Drug Screen (UDS) Positive for Opioids | Baseline UDS positive for opioids | 9 Participants |
| Extended Release Naltrexone | Number of Participants With Urine Drug Screen (UDS) Positive for Opioids | 16 weeks UDS positive for opioids | 4 Participants |
Secondary
Number of Participants With Urine Ethyl Glucuronide (EtG) Positive for Alcohol
Time frame: Baseline and 16 weeks
Population: In both the TAU and XR-NTX groups, reporting results for participants who were retained at 16 weeks and completed necessary study assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment as Usual | Number of Participants With Urine Ethyl Glucuronide (EtG) Positive for Alcohol | Baseline EtG positive for alcohol | 7 Participants |
| Treatment as Usual | Number of Participants With Urine Ethyl Glucuronide (EtG) Positive for Alcohol | 16 weeks EtG positive for alcohol | 4 Participants |
| Extended Release Naltrexone | Number of Participants With Urine Ethyl Glucuronide (EtG) Positive for Alcohol | Baseline EtG positive for alcohol | 6 Participants |
| Extended Release Naltrexone | Number of Participants With Urine Ethyl Glucuronide (EtG) Positive for Alcohol | 16 weeks EtG positive for alcohol | 3 Participants |
Secondary
Participant Safety: Any Fatal or Non-fatal Overdose Between Baseline and Week 16
Time frame: 16 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment as Usual | Participant Safety: Any Fatal or Non-fatal Overdose Between Baseline and Week 16 | Nonfatal opioid overdose | 1 Participants |
| Treatment as Usual | Participant Safety: Any Fatal or Non-fatal Overdose Between Baseline and Week 16 | Fatal opioid overdose | 0 Participants |
| Extended Release Naltrexone | Participant Safety: Any Fatal or Non-fatal Overdose Between Baseline and Week 16 | Nonfatal opioid overdose | 1 Participants |
| Extended Release Naltrexone | Participant Safety: Any Fatal or Non-fatal Overdose Between Baseline and Week 16 | Fatal opioid overdose | 0 Participants |
Secondary
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
Time frame: Baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment as Usual | Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Mean AST at baseline | 32.3 IU/L | Standard Deviation 19.4 |
| Treatment as Usual | Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Mean AST at 16 weeks | 32.2 IU/L | Standard Deviation 17.6 |
| Treatment as Usual | Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Mean ALT at 16 weeks | 30.8 IU/L | Standard Deviation 18.1 |
| Treatment as Usual | Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Mean ALT at baseline | 33.0 IU/L | Standard Deviation 24.5 |
| Extended Release Naltrexone | Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Mean ALT at 16 weeks | 40.1 IU/L | Standard Deviation 38.4 |
| Extended Release Naltrexone | Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Mean AST at baseline | 36.8 IU/L | Standard Deviation 23.1 |
| Extended Release Naltrexone | Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Mean AST at 16 weeks | 38.8 IU/L | Standard Deviation 27.6 |
| Extended Release Naltrexone | Participant Safety: Change in Liver Enzymes Between Baseline and Week 16 | Mean ALT at baseline | 35.0 IU/L | Standard Deviation 35.6 |
Secondary
Participant Safety: Precipitated Withdrawal
Proportion of participants assigned to XR-NTX who develop precipitated opioid withdrawal.
Time frame: 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment as Usual | Participant Safety: Precipitated Withdrawal | 0 Participants |