St. PETERsburg Pain and Alcohol Intervention With Naltrexone and Nalmefene

Study Overview
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Brief Summary
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This study is a randomized controlled trial (RCT) to assess the feasibility, tolerability, and safety of using opioid receptor antagonists (naltrexone and nalmefene) to treat pain among HIV-infected persons with heavy alcohol use and chronic pain.

Detailed Description
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Pain is a common co-morbidity for HIV-infected patients. Prevalence studies suggest that, on average, half of all HIV-infected persons suffer pain. Chronic pain can lead to heavy alcohol use among HIV-infected 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. Opioid receptor antagonists such as naltrexone and nalmefene, which are licensed for treatment of alcohol use disorders, show promise as being effective and safe treatments for chronic pain among persons with HIV. This study will pilot test novel pharmacotherapies (opioid receptor antagonists) to improve chronic pain among HIV-infected heavy drinkers. The specific aims of the research is to assess the feasibility, tolerability and safety of using opioid receptor antagonists (low-dose naltrexone and nalmefene) to treat pain among HIV-infected persons with heavy alcohol use and chronic pain.

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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HIV Infection, Alcohol Use, Pain

Intervention / Treatment
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* Drug: Low dose naltrexone
* Drug: Nalmefene


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 Uncontrolled psychiatric illness (such as active psychosis) (i.e., answered yes to any of the following: past three month active hallucinations; mental health symptoms prompting a visit to the ED or hospital) History of hypersensitivity to naltrexone, nalmefene, 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 ALT/AST levels >5x normal History of Raynaud's Disease Planned surgeries in the next three months Enrolled in another HIV and/or substance use medication intervention study Taking naltrexone in the past 30 days Taking nalmefene in the past 30 days

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 |
| --- | --- |
| Experimental: 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<br>|
| Experimental: Nalmefene<br>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks. | Drug: Nalmefene<br>* 18 mg of nalmefene taken once daily for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication Tolerability Measured Via a 0-100 Visual Analog Scale | Medication tolerability will be measured via a 0-100 visual analog scale. Participants will be asked to indicate on a scale of 0-100, how well they have tolerated the study medication with 0 anchored as cannot tolerate at all and 100 as tolerate perfectly well. Higher numbers will be indicative of higher tolerability of the medication. | Primary endpoint at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks | Measured via 30 Day Alcohol Use Timeline Follow Back Method | Baseline, 8 weeks | 
| Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period | Measured via one question asking participants if they had discontinued medication since their last visit. Assessed at 4 and 8 week study visits. | 4 weeks, 8 weeks | 
| Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks | Measured by participants' drawing a line on a a Visual Analog Scale, which ranges from 0 to 100. Higher numbers indicate higher adherence to study medication. | Endpoint at 8 weeks | 
| Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence | Measured through visual inspection of the urine for the presence or absence of riboflavin using ultraviolet (UV) light at the long wave setting (33 mm) in a room with low ambient light. | Endpoint at 8 weeks | 
| Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | Measured via a 16-item symptom checklist with the option for participants to report any experienced side effects not on the checklist. Side effect severity is rated by trained research assessors. The checklist is asked at 2, 4, 6, and 8-week study visits. | 2 weeks, 4 weeks, 6 weeks, 8 weeks | 
| Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction. | Measured via using the 14-item Treatment Satisfaction Questionnaire, which consists of 14 items that result in four domains: Effectiveness, Side Effects, Convenience and Global Satisfaction. Higher scores indicate greater satisfaction with medication. Assessed at 4 and 8 week study visits. | 4 weeks, 8 weeks | 
| Severe Hepatotoxicity Defined as AST/ALT >10X the Level of Normal | Aminotransferase levels (AST/ALT) are tested to look for severe hepatotoxicity defined as AST/ALT > 10 times the level of normal. | Endpoint at 8 weeks | 

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