Naltrexone for Overdose Prevention

Phase 2

Recruiting

• Conditions: Overdose Accidental
• Interventions: Drug: IM naltrexone; Behavioral: Usual Care

• Registration Number: NCT06633900
• Lead Sponsor: University of California, San Francisco

Brief Summary

The goal of this clinical trial is to see if an injectable medicine called naltrexone can prevent fentanyl overdose deaths in people who use other drugs (cocaine, methamphetamine). The main questions it aims to answer are:

What are the challenges for implementing naltrexone as an overdose prevention strategy?

Are injections of naltrexone effective for opioid overdose prevention among people who use stimulants?

How often are people who use stimulants and do not intentionally use opioids unintentionally exposed to opioids?

Researchers will compare participants to receive the study medication to the usual care group to see if one group experiences fewer opioid overdose events than the other.

Participants will be randomized to either receive a monthly injection of naltrexone over six months, or receive usual care. Usual care includes harm reduction supplies. Laboratory procedures will include the collection of urine, blood, and hair samples for various safety and outcome measure testing.

Detailed Description

This pilot randomized controlled trial aims to evaluate the efficacy of IM naltrexone for opioid overdose prevention among individuals living with HIV (PWH) and those at risk for HIV who use stimulants. The study will concurrently collect data on the feasibility, acceptability, and preliminary effectiveness of the intervention, along with epidemiological data on the prevalence of both intentional and unintentional fentanyl exposure in this population.

Participants will be randomly assigned in a 1:1 fashion to either the intervention group, which will receive IM naltrexone, or the usual care group, which will be provided with safe consumption supplies and intranasal naloxone.

Monthly assessments over a 24-week period post-intake (followed by a final study visit at 32 weeks) will be conducted to measure participants' exposure to fentanyl/opioids, utilizing both short-term (urine) and long-term (hair) biomarkers, as well as self-reported data. Adherence to the monthly IM naltrexone injections and the safety profile of the 'opioid PrEP' will also be rigorously evaluated.

Study Timeline

• Study First Submitted: 2024-10-07
• Study First Submitted QC: 2024-10-07
• Study First Posted: 2024-10-09
• Status Verified: 2025-04
• Study Start: 2025-04-10
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-23
• Primary Completion: 2027-04-15
• Study Completion: 2027-04-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. at-risk for HIV or living with HIV
2. stimulant use disorder (by DSM-V) or positive urine drug test for cocaine, amphetamine, or methamphetamine in last 6 months AND report at least 10 days of stimulant use/month,
3. able to provide informed consent,
4. English-speaking,
5. age 18 years old or greater.

Exclusion Criteria

1. prescribed or non-prescribed opioid use (including newly diagnosed opioid use disorder by DSM-V),
2. receipt of long-acting injectable naltrexone for other indications in past 30 days,
3. planned surgery in next 6 months,
4. moderate, severe or chronic liver disease (AST, ALT ≥ 5 times the upper limit of normal or symptoms of current liver disease),
5. persons who are pregnant or breastfeeding,
6. increased risk of bleeding (thrombocytopenia <50 x 109/L, coagulopathy, or therapeutic anticoagulation), or
7. known hypersensitivity to naltrexone or its diluents.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	IM naltrexone	Participants assigned to the intervention arm will receive naltrexone injections once a month over 6 months. The naltrexone injection (380mg) will be administered every 4 weeks in the ventrogluteal location.
Control	Usual Care	Participants in the control arm will receive usual care.

Primary Outcome Measures

Name	Time	Method
Acceptability	6 months	The primary outcome is the acceptability of IM naltrexone as opioid PrEP, which the study investigators will quantitatively assess via retention in treatment at 24 weeks and proportion of on-time injections during the study period. The investigators will consider 50% of enrolled participants completing 3 or more injections to meet a minimum standard of intervention uptake.

Secondary Outcome Measures

Name	Time	Method
Effectiveness	6 months	The study investigators will also evaluate incident opioid overdose, which will be defined as 1) fatal overdose, 2) overdose requiring emergency medical services (including first-responder evaluation, emergency department visit, hospitalization), or 3) participant report of overdose or sedation responding to community-delivered naloxone. This will allow the investigators to define unintentional opioid overdose rates among PWH or individuals at risk only seeking to use stimulants (with inadvertent exposure to opioids) while also evaluating possible effectiveness of IM naltrexone as an augmented harm reduction strategy.
Safety	6 months	Our primary safety outcome is proportion of participants with grade 2 or worse adverse events (such as nausea, vomiting, laboratory abnormalities, neurologic symptoms).

Trial Locations

Locations (1)

Center on Substance Use and Health; 🇺🇸 San Francisco, California, United States