Rapid Naltrexone Initiation for Opioid Addiction

Overseen By Elias Dakwar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: New York State Psychiatric Institute

Must not be taking: Methadone, Buprenorphine, Psychotropics, Ritonavir

Disqualifiers: Alcohol dependence, Psychiatric disorders, Suicidal risk, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 10

Duration: 12 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a long-lasting injection to block opioid effects and another medication to ease withdrawal. It targets people with opioid addiction who have finished detox and are at risk of relapse. The treatment prevents opioids from affecting the brain and reduces withdrawal symptoms.

Will I have to stop taking my current medications?

The trial requires that participants not be on methadone or buprenorphine maintenance treatment, and they must not be taking psychotropic or other medications that might interact with the study medications. If you are on these medications, you may need to stop taking them to participate.

What data supports the effectiveness of the drug CI-581-a, CI-581-b for opioid addiction?

Naltrexone, a component of the treatment, is an opioid antagonist that has been shown to help reduce cravings and prevent relapse in opioid addiction when used in an extended-release form, which improves adherence compared to the oral form. ^{1 2 3 4 5}

Is naltrexone safe for human use?

Naltrexone has been studied for over three decades and is generally considered safe for human use, with minimal side effects like nausea and abdominal pain in some patients. However, high doses can cause liver damage, and there is a risk of opioid overdose if someone tries to overcome its effects by taking more opioids. ^{2 6 7 8 9}

How does the drug CI-581-a, CI-581-b differ from other treatments for opioid addiction?

The treatment involves rapid initiation of naltrexone, which is unique because it uses an extended-release injection form that only needs to be administered monthly, improving adherence compared to daily oral naltrexone. This approach is particularly beneficial for patients who struggle with daily medication compliance, offering a more consistent and effective way to manage opioid addiction. ^{2 4 10 11 12}

Research Team

Elias Dakwar, MD

Principal Investigator

NYSPI

Eligibility Criteria

This trial is for adults aged 18-70 with opioid use disorder for at least six months, confirmed by tests. Participants must be in good health as determined by medical exams and lab tests, not on conflicting medications, and interested in naltrexone treatment. Pregnant or breastfeeding women, those with certain psychiatric disorders or unstable physical conditions like severe hypertension or liver disease are excluded.

Inclusion Criteria

DSM-5 criteria of current opioid use disorder present for at least six months, supported by a positive urine for opioids or a positive naloxone challenge test

Able to give written informed consent to participate in the study

I am interested in taking extended-release naltrexone for maintenance.

Exclusion Criteria

I am not on medications that could react badly with the study drugs.

History of a use disorder with the study medications

I do not have uncontrolled high blood pressure, severe anemia, active liver disease, or untreated diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Detoxification and Washout

Participants undergo nonopioid detoxification and receive CI-581a or CI-581b during the washout phase

1 week

Inpatient treatment for up to 5 days

Naltrexone Titration

Naltrexone titration schedule is initiated with close monitoring to ensure tolerability

1 week

Inpatient treatment for up to 5 days

Treatment

Participants receive 12 weeks of mindfulness-based relapse prevention and motivational interviewing sessions

12 weeks

Twice weekly meetings with staff

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CI-581-a
• CI-581-b

Trial Overview The study is testing the effectiveness of two glutamate modulators (CI-581-a and CI-581-b) to quickly start patients on extended-release naltrexone without using opioids. It's a randomized controlled trial where participants receive one of the test drugs to see if it helps prevent relapse after detoxification from opioids.

Participant Groups

Group I: CI-581a Experimental Treatment 1 Intervention

CI-581a will be administered during the washout phase when participants are experiencing moderate withdrawal, as well as the following day when the naltrexone titration is initiated. (0.11 mg/kg 2-min bolus followed by 1.3 mg/kg over 90 min)

Group II: CI-581b Placebo Group 1 Intervention

CI-581b will be administered during the washout phase when participants are experiencing moderate withdrawal, as well as the following day when the naltrexone titration is initiated. (2-min saline bolus followed by 0.0125 mg/kg over 90 min)

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Naltrexone, an effective treatment for reducing alcohol cravings in individuals with alcohol use disorder (AUD), is significantly underutilized despite its proven safety and efficacy.

A quality improvement project aimed to enhance knowledge and prescribing practices for naltrexone, with goals to increase prescriptions for patients with AUD by 5% and achieve 50% staff participation in educational activities, indicating a proactive approach to improve treatment accessibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Education Intervention to Increase Naltrexone Use Among Adult Inpatients With Alcohol Use Disorder. Ipsarides, J.[2023]

The FDA-approved extended-release formulation of naltrexone, administered as a monthly injection, may improve adherence and retention rates in treating opioid dependence compared to the oral form, which has low compliance (less than 30%).

While naltrexone effectively reduces the rewarding effects of opioids to prevent relapse, there are safety concerns, including potential liver damage at high doses and risks of opioid overdose if individuals attempt to overcome the drug's antagonistic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone extended-release injection: an option for the management of opioid abuse. Taylor, R., Raffa, RB., Pergolizzi, JV.[2021]

In a 48-week study involving 200 participants with opioid addiction and HIV, the naltrexone implant group showed a significant improvement in maintaining viral loads below 400 copies per mL at 48 weeks compared to the oral naltrexone group, suggesting that long-acting naltrexone may enhance HIV treatment outcomes.

Despite some serious adverse events, including deaths in both groups, the study indicates that longer opioid blockade from the implant may help protect against missed antiretroviral therapy doses and impulsive behaviors that could lead to relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial. Krupitsky, E., Blokhina, E., Zvartau, E., et al.[2020]

Naltrexone is a safe and effective treatment option for heroin dependence, particularly for highly motivated individuals who are already opiate-free.

While naltrexone has minimal side effects, primarily gastrointestinal issues, patient compliance remains a challenge due to the lack of immediate consequences for discontinuing the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of heroin-dependent persons with antagonists: current status. Renault, PF.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Education Intervention to Increase Naltrexone Use Among Adult Inpatients With Alcohol Use Disorder. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Naltrexone extended-release injection: an option for the management of opioid abuse. [2021]

3. Hungary pubmed.ncbi.nlm.nih.gov

The use of naltrexone in pathological and problem gambling: A UK case series. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Naltrexone: its clinical utility. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Treatment of heroin-dependent persons with antagonists: current status. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

The safety profile of naltrexone in the treatment of alcoholism. Results from a multicenter usage study. The Naltrexone Usage Study Group. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Naltrexone in addicted business executives and physicians. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

A Randomized Trial Comparing Extended-Release Injectable Suspension and Oral Naltrexone, Both Combined With Behavioral Therapy, for the Treatment of Opioid Use Disorder. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Baseline characteristics of patients predicting suitability for rapid naltrexone induction. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Case report: Increasing the frequency of intramuscular naltrexone administration in a high risk patient with opioid use disorder. [2022]