St. PETERsburg Pain and Alcohol Intervention With Naltrexone and Nalmefene (PETER PAIN)

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Pain; Alcohol Use
• Intervention / Treatment: Drug: Low dose naltrexone; Drug: Nalmefene

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • St. Petersburg, Russian Federation, 197022
    • First St. Petersburg Pavlov State Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose naltrexone; Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.	Drug: Low dose naltrexone; 4.5 mg of low dose naltrexone taken once daily for 8 weeks
Experimental: Nalmefene; Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.	Drug: Nalmefene; 18 mg of nalmefene taken once daily for 8 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Jeffrey H. Samet, MD, MA, MPH, Boston University/Boston Medical Center

Publications and helpful links

General Publications

• Bendiks S, Cheng DM, Blokhina E, Vetrova M, Verbitskaya E, Gnatienko N, Bryant K, Krupitsky E, Samet JH, Tsui JI. Pilot study of tolerability and safety of opioid receptor antagonists as novel therapies for chronic pain among persons living with HIV with past year heavy drinking: a randomized controlled trial. AIDS Care. 2021 Mar 7:1-10. doi: 10.1080/09540121.2021.1896663. Online ahead of print.

Helpful Links

• URBAN ARCH, a member of NIAAA CHAART (Consortiums for HIV/AIDS & Alcohol Research Translation) initiative, conducts and disseminates interdisciplinary research on how alcohol impacts people with HIV and develops interventions to reduce related outcomes.

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2018
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): December 19, 2018

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 8, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: HIV; Pain; Low-dose naltrexone; Alcohol Use; Nalmefene
• Additional Relevant MeSH Terms: Drinking Behavior; Alcohol Drinking; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone; Nalmefene
• Other Study ID Numbers: H-36491; UH2AA026193 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All data from the study will be placed into the URBAN ARCH repository.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No