Intermittent Oral Naltrexone Enhanced With an Ecological Momentary Intervention for Methamphetamine-using MSM

NCT04791969 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 20-32912R01DA053171
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blind, placebo-controlled phase 2b trial in which 54 MSM who use meth will be randomly assigned (2:1) to receive 12 weeks of as-needed intermittent oral naltrexone 50 mg enhanced with an EMA-informed EMI platform, or receive as-needed placebo with EMA-informed EMI. The 12-week treatment period is consistent with other pharmacotherapy trials for substance use disorders. The proposed sample size is also consistent with other phase 2b trials for substance use treatment. Upon enrollment, participants will complete daily EMA assessments and weekly visits for behavioral surveys and urine testing for meth metabolites, study drug dispensing and computer-based counseling for substance use. Safety laboratory assessments and vital signs will be completed monthly. Efficacy (Specific Aims 1-3) will be assessed upon trial completion as measured by proportion meth-positive urine samples; PrEP and ART adherence by drug levels and viral load testing; and sexual risk behavior data accounting for PrEP use and viral suppression.

Conditions

Methamphetamine Use Disorder

Keywords

Methamphetamine; meth; naltrexone

Outcome Measures

Primary Outcomes (1)

• Number of People With Meth-positive Urine Tests at Weekly Visits

  As measured by the count of participants with meth-positive urine tests.

  Every week from week 1 to the end of treatment at 12 weeks

Secondary Outcomes (1)

• Mean in Sexual Risk Behaviors at Week 12

  Past month behavior, measured at the end of treatment at 12 weeks

Other Outcomes (1)

• Adherent to PrEP or to Antiretroviral Medication

  At the end of treatment at the 12-week visit

Study Arms (2)

Naltrexone with ecological momentary intervention

EXPERIMENTAL

Naltrexone Hydrochloride, 50 mg., intermittent with ecological momentary assessment (EMA)

Drug: Naltrexone Hydrochloride; Behavioral: Ecological Momentary Intervention

Placebo with ecological momentary intervention

PLACEBO COMPARATOR

Placebo, intermittent with ecological momentary assessment (EMA)

Drug: Placebo; Behavioral: Ecological Momentary Intervention

Interventions

Naltrexone Hydrochloride DRUG

Intermittent Oral Naltrexone, 50 mg

Also known as: ReVia

Naltrexone with ecological momentary intervention

Placebo DRUG

Intermittent Oral Placebo

Placebo with ecological momentary intervention

Ecological Momentary Intervention BEHAVIORAL

Receive ecological momentary intervention if ecological momentary assessment reports meth craving, stress, not taking study drug, or antecedents detected for "high risk" meth use.

Also known as: EMI

Naltrexone with ecological momentary intervention; Placebo with ecological momentary intervention

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: cisgender male, men who have sex with men
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• cisgender male (male gender and sex assigned at birth)
• age 18-70 years\* (naltrexone's tolerability and safety has been demonstrated among older adults up to age 70)
• self-reported condomless anal sex with men or missing Pre-Exposure Prophylaxis or antiretroviral therapy doses due to meth use in the prior three months while under the influence of meth
• self-reported meth use at least weekly
• mild, moderate or severe meth use disorder
• positive meth sample via sweat patch or urine testing during screening
• interested in reducing meth use
• no current acute illness requiring prolonged medical care
• no chronic illness that is likely to progress clinically during trial
• able and willing to provide informed consent and adhere to visit schedule
• current CD4 count ≥ 200 cells/mm3; or CD4 count of 100-199 cells/mm3 and HIV viral load \< 200 copies/mL (if living with HIV)
• baseline complete blood count, total protein, albumin, glucose, alkaline phosphatase, creatinine, blood urea nitrogen test, and electrolytes without clinically significant abnormalities as determined by study clinician in conjunction with symptoms, physical exam, and medical history

You may not qualify if:

• any psychiatric (e.g., depression with suicidal ideation) or medical condition that would preclude safe participation
• known allergy or prior adverse reaction to naltrexone
• current use of any opioids or a known medical condition which currently requires or may likely require opioid analgesics
• opioid-positive urine test at screen/enrollment visits (naltrexone can induce opioid withdrawal)
• moderate or severe liver disease (aspartate aminotransferase test, alanine aminotransferase test, or total bilirubin \> 3 times upper limit of normal)
• impaired renal function (creatinine clearance \< 60 ml/min)
• currently participating in another intervention research study with potential overlap
• severe alcohol use disorder as determined by structured clinical interview for DSM-5 criteria
• any condition that, in the PI and/or study clinician's judgment interferes with safe participation or adherence to study procedures

Sponsors & Collaborators

• Glenn-Milo Santos: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

San Francisco Department of Public Health

San Francisco, California, 94102, United States

Location

MeSH Terms

Interventions

Naltrexone

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

Limitations include loss to follow-up in study participants, leading to a smaller number of observations analyzed than original number of participants enrolled.

Results Point of Contact

• Title: Glenn-Milo Santos
• Organization: University of California San Francisco

glenn-milo.santos@ucsf.edu

(415) 476-1435

Study Officials

• Glenn-Milo Santos, PhD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind, placebo controlled 2b clinical trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: 2:1 Naltrexone with EMI vs. Placebo with EMI

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: March 10, 2021
• Study Start: December 14, 2021
• Primary Completion: March 1, 2024
• Study Completion: July 1, 2024
• Last Updated: October 27, 2025
• Results First Posted: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)