St. PETERsburg Pain and Alcohol Intervention With Naltrexone and Gabapentin

Study Overview
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Brief Summary
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This study is a 3-arm pilot, randomized, double-blinded, placebo-controlled study of low-dose naltrexone and gabapentin versus placebo among HIV-positive persons with heavy alcohol use and chronic pain to provide estimates of their effects on 1) pain; 2) inflammation; and 3) measures of HIV control. Participants will be followed for 12 weeks. Assessments of study outcomes will be compared at week 8 (end of treatment phase).

Detailed Description
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Pain is a common co-morbidity for HIV-positive patients.Prevalence studies suggest that, on average, half of all HIV-positive persons suffer pain. Chronic pain can lead to heavy alcohol use among HIV-positive persons, which may in turn be a barrier to treatment/control of HIV and contribute to spread of HIV. Thus there is an urgent need to address pain among persons with HIV. It is timely and relevant to conduct research on gabapentin, as it has emerged as one of the most commonly prescribed non-opioid medications for pain despite the fact that gabapentin is only FDA approved for post-herpetic neuralgia and the literature to support its use for generalized chronic pain is limited. And yet, gabapentin has demonstrated benefits for treatment of alcohol use disorder, and therefore, like naltrexone, it could have a specific role for treating patients with chronic pain and unhealthy alcohol use. This study is a 3-arm pilot, randomized, double-blinded, placebo-controlled study of low-dose naltrexone and gabapentin vs. placebo among HIV-positive persons with heavy alcohol use and chronic pain to provide estimates of their effects on 1) pain (both self-reported and experimental/cold pressor test; 2) inflammation (i.e., levels of inflammatory cytokines IL-6, IL-1β, IL-10, and TNF-α); and 3) measures of HIV control (CD4 count and viral load).

Official Title
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Pilot Study of Opioid-receptor Antagonists to Reduce Pain and Inflammation Among HIV-Infected Persons With Alcohol Problems

Conditions
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Chronic Pain, Alcohol Use, Unspecified, HIV Infections

Intervention / Treatment
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* Drug: Low-dose naltrexone
* Drug: Gabapentin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older HIV-positive Chronic pain (present ≥3 mo) of moderate to severe intensity Heavy drinking past year (Based on NIAAA criteria: > 14 standard drinks per week/ > 4 drinks in a day for men; > 7 drinks in the past week/ > 3 drinks in a day for women) If female, negative pregnancy test and willing to use adequate birth control Provision of contact information for 2 contacts to assist with follow-up Stable address within 100 kilometers of St. Petersburg Possession of a telephone (home or cell) Able and willing to comply with all study protocols and procedures Exclusion Criteria: Not fluent in Russian Cognitive impairment resulting in inability to provide informed consent based on research assessor (RA) assessment Known active TB or current febrile illness Breastfeeding Known uncontrolled psychiatric illness (such as active psychosis) Current suicidal ideation History of hypersensitivity to naltrexone, gabapentin, or naloxone Current use (past week) of illicit or prescribed opiates as documented by either self-report or positive urine drug test Unwilling to abstain from opiates during the treatment period Current use of neuroleptics History of seizure disorder Known liver failure AST/ALT levels >5x normal CrCl< 60mL/min History of Reynaud's disease Planned surgeries in the next 3 months Enrolled in another HIV and/or substance use medication intervention study Taking naltrexone in the past 30 days Taking gabapentin in the past 30 days Taking pregabalin in the past 30 days Diagnosis of chronic obstructive pulmonary disease (COPD)

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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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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low-dose naltrexone<br>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks. | Drug: Low-dose naltrexone<br>* 4.5 mg of low dose naltrexone taken once daily for 8 weeks. In week 1, participants will take 4.5mg of naltrexone once daily. In week 2, participants will take 4.5mg of naltrexone once daily, and a placebo capsule twice daily. In weeks 3 through 7, participants will take 1 placebo capsule with 4.5 mg mg of naltrexone once daily, and 2 placebo capsules twice daily. In week 8, in days 1-4 participants will take 4.5 mg of naltrexone with a placebo capsule once daily and 2 placebo capsules twice daily; in days 5-7, participants will take 4.5 mg of naltrexone once daily, and a placebo capsule twice daily.<br>|
| Active Comparator: Gabapentin<br>Participants randomized to the gabapentin arm begin on a dose of 300 mg daily (300 mg qd). In week 2, participants will take 300 mg of gabapentin three times daily. In week 3 the dose will be titrated up to 1800 mg daily (300 mg+300 mg tid) will remain on the dose until week 8, when they will be tapered back down to 900 mg daily (300 mg tid). In week 8, in days 1-4 participants will take 1800 mg daily (300 mg+300 mg tid); in days 5-7, participants will take 900 mg daily (300 mg of gabapentin three times daily). | Drug: Gabapentin<br>* Dose will begin at 300 mg daily (300 mg qd), in week 2 the dose will be titrated up to 900 mg daily (300 mg tid). In week 3, the dose will be titrated to 1800 mg daily ( 2 capsules of 300 mg tid) and participants will remain on that dose until week 8. In week 8, in days 1-4 participants will take 1800 mg daily (300 mg+300 mg tid); in days 5-7, participants will take 900 mg daily (300 mg of gabapentin three times daily).<br>|
| Placebo Comparator: Placebo<br>Participants will receive a placebo to be taken three times daily for 8 weeks. | Drug: Placebo<br>* In week 1, participants will take 1 placebo capsule once daily. In week 2, participants will take 1 placebo capsule three times per day. In weeks 3 through 7, 2 placebo capsules three times per day. In week 8, in days 1-4 participants will take 2 placebo capsules three times per day; in days 5-7, participants will take 1 placebo capsule three times per day. The placebo medications will be composed of lactose and will not contain active ingredients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Past Week Pain Severity | Change in past week pain severity (score 0 [no pain] -10 [high pain]) from baseline to week 8. Pain severity will be measured using the Brief Pain Inventory, which allows patients to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function | Baseline, 8-weeks | 
| Change in Past Week Pain Interference | Change in past week pain interference (score 0 [no pain]-10 [high pain]) from baseline to week 8. Pain interference will be measured using the Brief Pain Inventory, which allows patients to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function | Baseline, 8-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cold Pain Tolerance | Mean change in the number of seconds a participant can keep their hand submerged in a container of iced water. Participants were instructed to keep their hand in as long as they could, up to 3 minutes. | Baseline, 8-weeks | 
| Change in Percentage of Past Month Heavy Drinking Days | Mean percentage of change in self-reported heavy drinking in the past 30 days of alcohol consumption obtained via the Timeline Followback (TLFB) method. The NIAAA definition of heavy drinking is used (> 4 drinks in a day for men; > 3 drinks in a day for women). Participants were asked about their alcohol consumption on each day in the previous 30 days. | Baseline, 8-weeks | 
| Change in CD4 Count | Defined as mean change in CD4 values from lab assay | Baseline, 8-weeks | 
| Number of Participants With a Change in HIV Viral Load Suppression Status | Defined as number of participants who change from suppressed to unsuppressed or unsuppressed to suppressed from lab tests | Baseline, 8-weeks | 
| Change in Biomarker IL-6 | Mean change in IL-6 values measured on blood samples collected using commercially available enzyme-linked immunosorbent assay kits (R&D Systems). | Baseline, 8-weeks | 
| Change in Biomarker IL-10 | Mean change in IL-10 values measured on blood samples collected using commercially available enzyme-linked immunosorbent assay kits (R&D Systems). | Baseline, 8 weeks | 
| Change in TNF-alpha | Mean change in TNF-alpha values measured on blood samples collected using commercially available enzyme-linked immunosorbent assay kits (R&D Systems). | Baseline, 8-weeks | 
| Change in IL-1beta | Mean change in IL-1beta values measured on blood samples collected using commercially available enzyme-linked immunosorbent assay kits (R&D Systems). | Baseline, 8-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Alcohol, HIV, Inflammation, Low-dose naltrexone, Gabapentin