Naltrexone for Drug Overdose Prevention

(NOD Trial)

Overseen By Xochitl Luna Marti, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of California, San Francisco

Must not be taking: Opioids, Anticoagulants

Disqualifiers: Liver disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 32

Duration: 24 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether an injectable medicine called naltrexone can help prevent fentanyl overdose deaths in individuals who use drugs like cocaine or methamphetamine. Participants will receive either a monthly naltrexone injection for six months or continue with their usual care, which includes harm reduction supplies. The trial aims to determine if naltrexone reduces overdose events compared to usual care. Individuals with a stimulant use disorder who frequently use drugs like cocaine or methamphetamine might be suitable for this trial. As a Phase 2/3 trial, this study assesses naltrexone's effectiveness and represents the final step before FDA approval, offering participants a chance to contribute to potentially life-saving research.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are using opioids or have been prescribed long-acting injectable naltrexone in the past 30 days, you cannot participate in the trial.

Is there any evidence suggesting that naltrexone is likely to be safe for humans?

Research has shown that naltrexone, the treatment used in this trial, has been studied for its safety in people. One study found no overdose cases in the group using extended-release naltrexone, while seven occurred in a group receiving usual treatment. This suggests that naltrexone might help prevent overdoses.

However, it is important to note that attempting to counteract naltrexone by taking large amounts of opioids can cause a serious overdose. Patients should be aware of this risk.

Overall, naltrexone is generally well-tolerated and has been used to help prevent opioid relapses. This trial explores its potential benefits in preventing fentanyl overdoses in people who use other substances. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Naltrexone is unique because it offers a preventative approach to drug overdoses by blocking the effects of opioids. Unlike standard treatments like naloxone, which is used to reverse an overdose once it occurs, naltrexone works by preventing the high from happening in the first place. This long-acting injection is administered once a month, which is more convenient and consistent compared to daily medications. Researchers are excited about naltrexone because it could significantly reduce the risk of overdose by removing the incentive to use opioids.

What evidence suggests that naltrexone might be an effective treatment for preventing opioid overdose?

Research has shown that naltrexone, administered as a monthly injection, can help prevent relapse into opioid use. One study found that receiving six monthly shots of extended-release naltrexone significantly reduced the likelihood of returning to opioid use compared to not receiving the treatment. In this trial, participants in the intervention arm will receive naltrexone injections once a month for six months. Naltrexone blocks the brain's opioid receptors, stopping the "high" and reducing cravings. This trial focuses on preventing fentanyl overdoses in individuals who use other drugs like cocaine and methamphetamine. Evidence suggests that naltrexone could lower the risk of overdose by blocking the effects of any opioids taken accidentally. These findings support the idea that naltrexone can effectively prevent harm related to opioid use. ^{1 2 3 4 6}

Who Is on the Research Team?

Ayesha Appa, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for people who use stimulants like cocaine or methamphetamine and are at risk of unintentional opioid exposure, specifically fentanyl. Participants must be willing to undergo monthly injections and provide urine, blood, and hair samples for testing.

Inclusion Criteria

Able to provide informed consent

Stimulant use disorder (by SCID-5) or positive urine drug test for cocaine, amphetamine, or methamphetamine in last 6 months AND report at least 10 days of stimulant use/month

I am at risk for HIV or currently living with HIV.

Exclusion Criteria

Buttock implants or fillers

I use opioids, prescribed or not, or have been newly diagnosed with an opioid use disorder.

Known hypersensitivity to naltrexone or its diluents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive monthly injections of naltrexone or usual care over a 6-month period

24 weeks

Monthly visits for injections and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Final study visit at 32 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone

Trial Overview The study tests if injectable naltrexone can prevent opioid overdoses in stimulant users not intentionally using opioids. It compares the effectiveness of monthly naltrexone injections against usual care (harm reduction supplies) over six months.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

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.

Group II: Control Active Control 1 Intervention

Participants in the control arm will receive usual care.

Naltrexone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vivitrol for:

• Alcohol dependence
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Opioid dependence
• Alcohol dependence

Approved in Canada as Vivitrol for:

• Opioid use disorder
• Alcohol dependence

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

A review of 263 cases related to Vivitrol (extended-release naltrexone) found that 84.6% of fatal overdoses occurred within two months after the last injection, highlighting a critical period for overdose risk.

The study suggests that there may be a link between Vivitrol discontinuation and increased overdose risk, indicating the need for further investigation and monitoring during this time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. Saucier, R., Wolfe, D., Dasgupta, N.[2019]

A study involving 250 opioid-dependent patients, many of whom had chronic hepatitis C virus (HCV) and HIV, found that intramuscular extended-release naltrexone (XR-NTX) did not significantly increase liver enzyme levels compared to a placebo, indicating its safety in this population.

Even though some patients experienced elevated liver enzymes, these levels improved over time, and no specific symptoms were linked to these elevations, suggesting that XR-NTX can be safely administered to patients with mild to moderate chronic HCV and/or HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. Mitchell, MC., Memisoglu, A., Silverman, BL.[2019]

In a 1-year open-label extension study involving 114 patients, injectable extended-release naltrexone (XR-NTX) demonstrated long-term efficacy, with 50.9% of participants remaining abstinent from opioids throughout the study.

The treatment was generally safe, with only 21.1% of patients reporting adverse events and no severe adverse events noted, although 16.7% experienced elevated liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. Krupitsky, EM., Nunes, EV., Ling, W., et al.[2016]

Induction success for extended-release naltrexone (XR-NTX) is significantly lower in individuals requiring opioid detoxification (62.6%) compared to those already detoxified (85.0%), indicating that detoxification status is crucial for treatment initiation.

Adherence to XR-NTX is relatively low, with only 44.2% of individuals completing all scheduled injections, and adherence rates are notably higher in controlled research settings compared to routine care, which limits the overall effectiveness of XR-NTX in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release injectable naltrexone for opioid use disorder: a systematic review. Jarvis, BP., Holtyn, AF., Subramaniam, S., et al.[2019]

In a study of 46,846 individuals with opioid use disorder, buprenorphine treatment significantly reduced the risk of opioid-related overdose compared to no treatment, with an adjusted hazard ratio of 0.40.

In contrast, both extended-release injectable and oral naltrexone did not show a significant reduction in overdose risk, indicating that buprenorphine may be a more effective option for preventing overdoses in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort. Morgan, JR., Schackman, BR., Weinstein, ZM., et al.[2022]

Heroin overdoses have become more common, with risk factors including recent abstinence and polydrug use, highlighting the urgent need for effective prevention strategies.

Naloxone is a safe and effective treatment for reversing heroin overdose effects, as it quickly counteracts respiratory depression and sedation, making it a crucial tool for overdose prevention in communities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription naloxone: a novel approach to heroin overdose prevention. Sporer, KA., Kral, AH.[2022]

The sustained release naltrexone implant significantly reduced opioid overdoses in a cohort of 361 heroin-dependent individuals, with no overdoses reported in the 6 months following treatment, compared to 21 overdoses in the 6 months prior.

While the implant effectively prevented opioid overdoses, there was an increase in sedative overdoses shortly after treatment, highlighting the need for comprehensive management of poly-substance use among heroin users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing hospital presentations for opioid overdose in patients treated with sustained release naltrexone implants. Hulse, GK., Tait, RJ., Comer, SD., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6366853/

Potential Risk Windows for Opioid Overdose Related to ... In a randomized trial (n=570) comparing the effectiveness of buprenorphine-naloxone with extended-release naltrexone, 15 individuals had 18 overdose events in ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2818410

Rapid Initiation of Injection Naltrexone for Opioid Use ... The XR-naltrexone (Vivitrol; Alkermes Inc) prescribing information recommends a 7- to 10-day opioid-free period before administering XR- ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1505409

Extended-Release Naltrexone to Prevent Opioid Relapse ... This open-label, randomized, controlled effectiveness trial compared six monthly injections of extended-release naltrexone (Vivitrol, Alkermes) ...

4. vivitrolhcp.com vivitrolhcp.com/alcohol-dependence-pivotal-study

Alcohol Dependence: VIVITROL ® Efficacy and Safety Data Find efficacy data from a VIVITROL® (naltrexone for extended-release injectable suspension) pivotal study.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06633900?cond=opioid%20overdose&aggFilters=status:not%20rec&rank=8

NCT06633900 | Naltrexone for Overdose Prevention This pilot randomized controlled trial aims to evaluate the efficacy of IM naltrexone for opioid overdose prevention among individuals living with HIV (PWH) and ...

6. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)00113-7/fulltext

Misclassification of overdose events in the X:BOT study The risk of overdose with naltrexone results when patients try to overcome μ-opioid receptor antagonism by taking increasingly high doses of ...