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

ABSTRACT

Pain is common and associated with substance use among persons with HIV (PWH), yet limited management strategies exist. We assessed the feasibility, tolerability, and safety of low-dose naltrexone and standard dose nalmefene to treat chronic pain among PWH with past-year heavy alcohol use in a randomized, double-blinded, 2-arm study (planned enrollment 8 per arm). Participants were recruited in St. Petersburg, Russia between May and October 2018 and randomized to receive either nalmefene (16 mg) or low-dose naltrexone (4.5 mg) for 8 weeks. The primary outcome was tolerability of medication at eight weeks. Study visits included assessments of pain interference and severity, as well as cold-pressor testing. All participants in the nalmefene arm (N = 3) discontinued the study medication early due to side effects; nalmefene was subsequently deemed intolerable and this arm was terminated. The mean tolerability score at 8-weeks in the low-dose naltrexone arm was 90.7 (SD 22.44), median was 100 (IQR 95- 100), and median cold pain tolerance was approximately 10 s higher at the end of the 8 weeks. Low-dose naltrexone was well-tolerated, but nalmefene was not, in this sample. Further research is warranted to explore low-dose naltrexone’s potential efficacy as a non-addictive treatment for pain in this population.

Clinical trial registration

ClinicalTrials.gov identifier: NCT03278886.

KEYWORDS:

• Pain
• HIV
• alcohol
• naltrexone
• nalmefene

Acknowledgements

The authors thank members of the URBAN ARCH Data and Safety Monitoring Board, Theodore Colton (Chair), Josiah Rich, Jesse Stewart, for their guidance and oversight of the PETER PAIN study. This work was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) under Grant UH2AA026193, U24AA020779, U24AA020778; and the Providence/Boston Center for AIDS Research P30AI042853. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health.

Disclosure statement

An employee of the funder (K. Bryant) is a co-author on this manuscript and helped guide analysis, interpretation and presentation of data and participated in the decision to submit the manuscript for publication. D. Cheng serves on Data Safety Monitoring Boards for Janssen Research & Development. The remaining authors report no declarations of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author, JT, upon reasonable request.

Additional information

Funding

This work was supported by the National Institute on Alcohol Abuse and Alcoholism and National Institute of Allergy and Infectious Diseases [grant numbers: UH2AA026193, U24AA020778, U24AA020779, P30AI042853].