Overdose AccidentalPhase 2/3NODNCT06633900
Naltrexone for Overdose Prevention
A Phase 2/3 study testing IM naltrexone in people with Overdose Accidental, run by University of California, San Francisco at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Overdose Accidental
- What is being tested?
- IM naltrexone
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2025to 15 Apr 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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),
- known hypersensitivity to naltrexone or its diluents, or
- any other reason (e.g. comorbid medical conditions, adherence concerns, lack of interest in naltrexone, etc.) that judged by the study team's discretion, would impede the participant from successfully completing the trial.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Center on Substance Use and Health
San Francisco, California, 94102
John Walker, RN, FNP-C, 628-217-6227, john.e.walker@sfdph.org
Xochitl Luna Marti, MPH, 628-217-6235, xochitl.lunamarti@sfdph.org
About this study
Official title: Extended-Release Naltrexone as Opioid Overdose Pre-Exposure Prophylaxis (PrEP) in People Using Stimulants Living With or At Risk of HIV
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?
Read more
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.
Read the 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.
- Conditions
- Overdose Accidental
- Being tested
- IM naltrexone, Usual Care
- Keywords
- stimulants, cocaine, methamphetamine, overdose prevention, naltrexone, fentanyl exposure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IM naltrexoneDrug
The study drug is an intramuscular injection of naltrexone (380mg), administered every 4 weeks via an injection in the ventrogluteal region.
Usual CareBehavioural
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.)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: IM naltrexone |
| Control | Active comparator | Participants in the control arm will receive usual care. Receives: Behavioral: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (2)
Effectiveness
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.
Measured: 6 months
Safety: Occurrence of Grade 2 or Worse Adverse Events
Our primary safety outcome is proportion of participants with grade 2 or worse adverse events (such as nausea, vomiting, laboratory abnormalities, neurologic symptoms).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2024
- Study start10 Apr 2025
- Primary completion15 Apr 2027 (estimated)
- Study completion15 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Overdose AccidentalStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to either receive the study medication or usual care.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Ayesha Appa, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06633900
- Sponsor's protocol ID
- 24-41278
- Other IDs
- 1DP2DA060600-01
- Acronym
- NOD
- Status last verified
- Jun 2026
- First submitted
- 7 Oct 2024
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extended-Release Naltrexone as Opioid Overdose Pre-Exposure Prophylaxis (PrEP) in People Using Stimulants Living With or At Risk of HIV
- ClinicalTrials.gov ID
- NCT06633900
- Acronym / sponsor ID
- NOD / 24-41278
- Conditions
- Overdose Accidental
- Keywords
- stimulants, cocaine, methamphetamine, overdose prevention, naltrexone, fentanyl exposure
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 10 Apr 2025 (actual)
- Primary completion
- 15 Apr 2027 (estimated)
- Study completion
- 15 Apr 2027 (estimated)
- First posted
- 9 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be randomized to either receive the study medication or usual care.
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: IM naltrexoneParticipants 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 | Active comparator | Behavioral: Usual CareParticipants in the control arm will receive usual care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IM naltrexoneThe study drug is an intramuscular injection of naltrexone (380mg), administered every 4 weeks via an injection in the ventrogluteal region. | Drug | Intervention |
| Usual CareParticipants 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.) | Behavioural | Control |
Primary outcome
Acceptability
Time frame: 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.
2 secondary outcomes
Effectiveness
Time frame: 6 months
Safety: Occurrence of Grade 2 or Worse Adverse Events
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Overdose Accidental
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Remote Intervention to Prevent Overdose
Accidental Overdose of Opiate
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Behavioral Safety and Fentanyl Education: BSAFE
Drug Overdose, Drug Overdose Accidental
Recruiting
Families Left Behind
Grief, Grief Disorder, Prolonged
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ayesha Appa, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing IM naltrexone in people with Overdose Accidental, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ayesha Appa, MD (628-206-7839, ayesha.appa@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acceptability (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.