Naltrexone for Overdose Prevention

NCT06633900 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 24-412781DP2DA060600-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Overdose Accidental

Keywords

stimulants; cocaine; methamphetamine; overdose prevention; naltrexone; fentanyl exposure

Outcome Measures

Primary Outcomes (1)

• Acceptability

  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.

  6 months

Secondary Outcomes (2)

• Effectiveness

  6 months

• Safety: Occurrence of Grade 2 or Worse Adverse Events

  6 months

Other Outcomes (2)

• Opioid exposure

  6 months

• Viral suppression

  6 months

Study Arms (2)

Intervention

EXPERIMENTAL

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.

Drug: IM naltrexone

Control

ACTIVE COMPARATOR

Participants in the control arm will receive usual care.

Behavioral: Usual Care

Interventions

IM naltrexone DRUG

The study drug is an intramuscular injection of naltrexone (380mg), administered every 4 weeks via an injection in the ventrogluteal region.

Intervention

Usual Care BEHAVIORAL

Participants assigned to usual care will receive a harm reduction bundle in clinic. It will include the following components: 1) intranasal naloxone 4mg x 2, 2) participant choice of safer consumption kits based on substances and route used (specific materials for inhaled use vs. injecting, based on common use practices in the region), 3) fentanyl test kits with 2 lateral flow assays per package along with instructions to minimize false positive results, and 4) information about universal overdose precautions (behavioral modifications to optimize safety like using in the presence of others, use a test dose of new substances, etc.)

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• at-risk for HIV or living with HIV
• 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,
• able to provide informed consent,
• English-speaking,
• age 18 years old or greater.

You may not qualify if:

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

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): collaborator
• University of California, San Francisco: lead

Study Sites (1)

Center on Substance Use and Health

San Francisco, California, 94102, United States

RECRUITING

Study Officials

• Ayesha Appa, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ayesha Appa, MD

CONTACT

628-206-7839; ayesha.appa@ucsf.edu

Xochitl Luna Marti, MPH

CONTACT

628-217-6235; xochitl.lunamarti@sfdph.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to either receive the study medication or usual care.

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 9, 2024
• Study Start: April 10, 2025
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): April 15, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)