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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help individuals with opioid addiction begin treatment with naltrexone, a medication that blocks opioid effects. Researchers aim to determine if a new drug, CI-581-a or CI-581-b, can facilitate a quicker and more comfortable transition to naltrexone without using other opioids. Participants will receive either the new drug or a placebo (a non-active treatment) during the trial. The trial seeks individuals who have experienced opioid use disorder for at least six months and are interested in naltrexone treatment after detox. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

An earlier study tested the treatment called CI-581-a for safety in people. The study found that most participants handled the treatment well. Some experienced mild side effects like headaches and nausea, but these were not serious and didn't last long.

This is encouraging for those considering joining the trial. The current trial's advanced stage indicates some trust in the treatment's safety. More participants have used it without major problems. For concerns about side effects or how the treatment might affect you, consult the trial team. They can provide detailed information based on the latest research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for opioid addiction, which often involves gradual naltrexone initiation alongside treatments like methadone or buprenorphine, CI-581a offers a rapid initiation approach. Researchers are excited about CI-581a because it is administered during moderate withdrawal, potentially reducing the discomfort and delay associated with traditional methods. This treatment uses a specific dosing regimen (0.11 mg/kg 2-min bolus followed by 1.3 mg/kg over 90 min) that aims to swiftly transition patients to naltrexone, possibly improving adherence and outcomes. Meanwhile, CI-581b serves as a placebo comparator, helping researchers understand the true efficacy of CI-581a.

What evidence suggests that this trial's treatments could be effective for opioid addiction?

Research suggests that CI-581-a, which participants in this trial may receive, might help individuals start using naltrexone more quickly without first using opioids. Naltrexone blocks opioid effects for about four weeks, aiding in relapse prevention after detox. CI-581-a likely affects glutamate, a brain chemical involved in addiction, potentially easing and accelerating the start of naltrexone use. Although more information is still being gathered, this approach aims to alter brain chemistry to reduce withdrawal symptoms, potentially smoothing the transition for those with opioid use disorder. ^{1 6 7 8 9}

Who Is on the Research Team?

Elias Dakwar, MD

Principal Investigator

NYSPI

Are You a Good Fit for This Trial?

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

History of a use disorder with the study medications

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9543602/

The opioid use disorder core outcomes set (OUD–COS) for ... The opioid use disorder core outcomes set (OUD–COS) for treatment research: findings from a Delphi consensus study

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK553166/

Opioid Use Disorder: Evaluation and Management - NCBI - NIH Cognitive behavioral therapy is most effective if combined with medications; however, there are mixed results on its effectiveness.[12][24].

3. withpower.com withpower.com/trial/phase-3-opioid-related-disorders-10-2017-c5529

Rapid Naltrexone Initiation for Opioid Addiction 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 ...

4. cdc.gov cdc.gov/mmwr/volumes/73/wr/pdfs/mm7325a1-H.pdf

Treatment for Opioid Use Disorder: Population Estimates The percentage of adults who needed OUD treatment was elevated among those who, during the previous year, had any mental illness (9.0%), used.

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2793293

Long-term Risk of Overdose or Mental Health Crisis After ... These findings suggest that opioid tapering was associated with increased rates of overdose, withdrawal, and mental health crisis extending up to 2 years after ...

6. psychiatry.org psychiatry.org/patients-families/opioid-use-disorder

Psychiatry.org - Opioid Use Disorder An estimated 3-12% of people treated with opioids for chronic pain will develop an addiction or abuse with negative consequences.(12) Approximately 8.6 million ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1526590018306229

Development of the Revised Opioid Risk Tool to Predict ... A score of 2 or lower indicates low risk for future opioid use disorder; a score of >/= 3 indicates high risk for opioid use disorder. Mark each box that ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK458655/

Pain Management and the Opioid Epidemic - NCBI Bookshelf With regard to the risks associated with the use of prescription opioids, it has been shown that once patients have been taking opioids longer than 90 days, the ...

9. library.samhsa.gov library.samhsa.gov/product/overdose-prevention-response-toolkit/pep23-03-00-001

Overdose Prevention and Response Toolkit SAMHSA's updated Overdose Prevention and Response Toolkit provides guidance to a wide range of individuals on preventing and responding to an overdose.