Pharmacotherapy Strategies for Opioid Use Disorder

Recruiting in Palo Alto (17 mi)

+25 other locations

Overseen by Roger Weiss, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: NYU Langone Health

Must be taking: Buprenorphine, Naltrexone

Must not be taking: Methadone, Opioids

Disqualifiers: Severe psychiatric, Alcohol use, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a two phase study investigating combinations of pharmacological and behavioral interventions to optimize the treatment of Opioid Use Disorder (OUD). The Retention Phase will assess strategies for improving retention on buprenorphine (BUP) and extended-release injectable naltrexone (XR-NTX). The Discontinuation Phase will assess which approaches are most likely to lead to long-term success (absence of relapse), and what characteristics of participants distinguish those who can safely discontinue Medications for Opioid Use Disorder (MOUD) from those who remain at risk of relapse and should not discontinue.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on methadone or have a serious medical or psychiatric condition that requires different care, you may not be eligible to participate.

What data supports the effectiveness of this drug for opioid use disorder?

Research shows that buprenorphine, especially in extended-release forms like Sublocade, helps reduce opioid use and improve treatment retention. Additionally, combining buprenorphine with naloxone (as in Suboxone) is effective in managing opioid use disorder by reducing misuse and increasing safety.

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Is the treatment for opioid use disorder safe for humans?

Buprenorphine, used in various forms like Suboxone and Sublocade, is generally considered safe for treating opioid use disorder, with a lower risk of overdose compared to methadone. However, it can still pose risks such as withdrawal and misuse, and some forms require surgical procedures for implantation.

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How is the drug SL-BUP, XR-NTX unique for treating opioid use disorder?

SL-BUP, XR-NTX combines buprenorphine, which partially activates opioid receptors to reduce cravings, with naltrexone, which blocks these receptors to prevent misuse. This combination offers a unique approach by using both a partial agonist and an antagonist, potentially improving adherence and reducing the risk of misuse compared to other treatments.

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Eligibility Criteria

Adults with opioid use disorder seeking treatment can join this study. They must be in stable health, speak English, and women should use birth control if applicable. Excluded are those with severe medical or mental conditions, certain substance dependencies, legal constraints that prevent participation, or who have used specific mHealth apps recently.

Inclusion Criteria

In good-enough general health (meaning good enough health to be in outpatient treatment) as determined by the study medical clinician on the basis of medical history, review of systems, and physical/mental status exam, to permit treatment with XR-NTX or BUP

Willing and able to provide written informed consent

I am looking for treatment for opioid addiction and considering buprenorphine or naltrexone.

Exclusion Criteria

Serious medical, psychiatric, or co-occurring substance use disorder or concomitant medication that, in the opinion of the study medical clinician, makes the patient not appropriate for outpatient treatment with buprenorphine or XR-NTX, but instead requires a higher or different level of care. Examples include: Disabling or terminal medical illness (e.g., uncompensated heart failure, cirrhosis or end-stage liver disease) as assessed by medical history, review of systems, physical exam and/or laboratory assessments; Severe, untreated or inadequately treated psychiatric condition (e.g., active psychosis, uncontrolled bipolar disorder) as assessed by history and/or clinical interview, requiring a different level of care (e.g., hospitalization); Current severe alcohol, benzodiazepine, or other depressant or sedative hypnotic use, requiring a different level of care (e.g., hospitalization); Suicidal or homicidal ideation or behavior requiring a different level of care (e.g., hospitalization); Known allergy or sensitivity to preferred medication or its components; Maintenance on methadone at the time of signing consent; For those preferring XR-NTX, presence of pain of sufficient severity as to require ongoing pain management with opioids; For those preferring XR-NTX, body habitus that, in the judgment of the study physician, precludes safe intramuscular injection of XR-NTX (e.g., BMI>40, excess fat tissue over the buttocks, emaciation); If female, currently pregnant or breastfeeding or planning on conception; Are currently in jail, prison or other overnight facility as required by court of law or have pending legal action that could prevent participation in study activities; Have used the reSET or reSET-O mHealth apps in the 3 months prior to consent; Other major reasons that might prevent an individual from participating in the study (e.g., a planned move out of the area)

Serious medical or psychiatric disorder or concomitant medication that, in the opinion of the study medical clinician, would make study participation hazardous to the participant or compromise study findings or would prevent the participant from completing the study. Examples include: Disabling or terminal medical illness (e.g., uncompensated heart failure, cirrhosis or end-stage liver disease) as assessed by medical history, review of systems, physical exam and/or laboratory assessments; Severe, untreated, or inadequately treated psychiatric condition (e.g., active psychosis, uncontrolled bipolar disorder) as assessed by history and/or clinical interview, requiring a different level of care (e.g., hospitalization); Suicidal or homicidal ideation or behavior requiring a different level of care (e.g., hospitalization); For participants entering the study taking buprenorphine, presence of pain requiring or likely requiring ongoing pain management with buprenorphine or other opioids; If female, currently pregnant or breastfeeding or planning on conception; Use of opioids (other than buprenorphine), cocaine, methamphetamine, or non-prescribed benzodiazepines in the past 12 weeks; Meets current DSM-5 criteria for any current alcohol use disorder; Are currently in jail, prison or other overnight facility as required by court of law or have pending legal action that could prevent participation in study activities; Have used the Connections mHealth app in the 3 months prior to consent; Other major reasons that might prevent an individual from participating in the study (e.g., a planned move out of the area)

I want to stop my medication for opioid use disorder after talking with my doctor.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Retention Phase

Strategies to improve retention in treatment on medications for opioid use disorder (MOUD) are tested.

26 weeks

Weekly visits (in-person or virtual)

Discontinuation Phase

Approaches to safely discontinue MOUD and achieve long-term success without relapse are assessed.

24-48 weeks

Bi-weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation.

24 weeks

Monthly visits (in-person or virtual)

Participant Groups

The trial is testing combinations of medications like buprenorphine (BUP) and extended-release naltrexone (XR-NTX), along with behavioral strategies to improve retention in treatment for opioid addiction and to determine safe discontinuation methods for long-term success without relapse.

Group I: Retention: XR-NTX + MMR Experimental Treatment 2 Interventions

Extended-release injectable naltrexone (XR-NTX) plus MMR, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group II: Retention: XR-NTX + MM Experimental Treatment 2 Interventions

Extended-release injectable naltrexone (XR-NTX) plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group III: Retention: XR-BUP + MMR Experimental Treatment 2 Interventions

Extended-release injectable buprenorphine (XR-BUP) plus MMR, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group IV: Retention: XR-BUP + MM Experimental Treatment 2 Interventions

Extended-release injectable buprenorphine (XR-BUP) plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group V: Retention: SL-BUP standard dose + MMR Experimental Treatment 2 Interventions

Standard dose sublingual buprenorphine-naloxone (SL-BUP) 16mg/day target plus MMR, consisting of Medical Management and usual counseling, plus a technology-based behavioral component.

Group VI: Retention: SL-BUP standard dose + MM Experimental Treatment 2 Interventions

Standard dose sublingual buprenorphine-naloxone (SL-BUP) 16mg/day target plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group VII: Retention: SL-BUP high dose + MMR Experimental Treatment 2 Interventions

High dose sublingual buprenorphine-naloxone (SL-BUP) 32mg/day target plus MMR, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group VIII: Retention: SL-BUP high dose + MM Experimental Treatment 2 Interventions

High dose sublingual buprenorphine-naloxone (SL-BUP) 32mg/day target plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group IX: Discontinuation: Discontinue XR-NTX with XR-NTX + MMD Experimental Treatment 2 Interventions

Start on XR-NTX, taper with XR-NTX, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group X: Discontinuation: Discontinue XR-NTX with XR-NTX + MM Experimental Treatment 2 Interventions

Start on XR-NTX, taper with XR-NTX, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group XI: Discontinuation: Discontinue XR-BUP with XR-BUP + MMD Experimental Treatment 2 Interventions

Start on XR-BUP, taper with XR-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group XII: Discontinuation: Discontinue XR-BUP with XR-BUP + MM Experimental Treatment 2 Interventions

Start on XR-BUP, taper with XR-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group XIII: Discontinuation: Discontinue SL-BUP with XR-BUP + MMD Experimental Treatment 2 Interventions

Start on SL-BUP, taper with XR-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group XIV: Discontinuation: Discontinue SL-BUP with XR-BUP + MM Experimental Treatment 2 Interventions

Start on SL-BUP, taper with XR-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

Group XV: Discontinuation: Discontinue SL-BUP with SL-BUP + MMD Experimental Treatment 2 Interventions

Start on SL-BUP, taper with SL-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.

Group XVI: Discontinuation: Discontinue SL-BUP with SL-BUP + MM Experimental Treatment 2 Interventions

Start on SL-BUP, taper with SL-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.

SL-BUP is already approved in European Union, United States, Canada, Australia for the following indications:

🇪🇺 Approved in European Union as Suboxone for:

• Opioid use disorder

🇺🇸 Approved in United States as Suboxone for:

• Opioid use disorder

🇨🇦 Approved in Canada as Suboxone for:

• Opioid use disorder

🇦🇺 Approved in Australia as Suboxone for:

• Opioid use disorder

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Dartmouth Hitchcock - ATP Lebanon, NH

Center for Psychiatric and Chemical Dependency Services (CPCDS) Pittsburgh, PA

Internal Medicine Recovery Engagement Program (IM-REP) Pittsburgh, PA

Shoreline Behavioral Health Services Conway, SC

More Trial Locations

Who Is Running the Clinical Trial?

NYU Langone Health Lead Sponsor

New York State Psychiatric Institute Collaborator

Columbia University Collaborator

Harvard Medical School (HMS and HSDM) Collaborator

Mclean Hospital Collaborator

National Institute on Drug Abuse (NIDA) Collaborator

The Emmes Company, LLC Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. [2018] To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

2. Netherlands pubmed.ncbi.nlm.nih.gov

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings. [2023] This analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE).

3. England pubmed.ncbi.nlm.nih.gov

Does Prescription Length of Buprenorphine Influence Treatment Outcomes in Opioid Use Disorder? A Retrospective Cohort Study from North India. [2023] Buprenorphine (BUP) effectively suppresses non-prescription opioid use and increases treatment retention in opioid use disorder (OUD). However, short prescription length may interfere with treatment retention and recovery. We wanted to examine whether the outcomes of BUP treatment differ in high (HPL up to 4 wk) and low-prescription (LPL 1-2 wk) length groups.

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

Selective review and commentary on emerging pharmacotherapies for opioid addiction. [2021] Pharmacotherapies for opioid addiction under active development in the US include lofexidine (primarily for managing withdrawal symptoms) and Probuphine®, a distinctive mode of delivering buprenorphine for six months, thus relieving patients, clinicians, and regulatory personnel from most concerns about diversion, misuse, and unintended exposure in children. In addition, two recently approved formulations of previously proven medications are in early phases of implementation. The sublingual film form of buprenorphine + naloxone (Suboxone®) provides a less divertible, more quickly administered, more child-proof version than the buprenorphine + naloxone sublingual tablet. The injectable depot form of naltrexone (Vivitrol®) ensures consistent opioid receptor blockade for one month between administrations, removing concerns about medication compliance. The clinical implications of these developments have attracted increasing attention from clinicians and policymakers in the US and around the world, especially given that human immunodeficiency virus/acquired immunodeficiency syndrome and other infectious diseases are recognized as companions to opioid addiction, commanding more efforts to reduce opioid addiction. While research and practice improvement efforts continue, reluctance to adopt new medications and procedures can be expected, especially considerations in the regulatory process and in the course of implementation. Best practices and improved outcomes will ultimately emerge from continued development efforts that reflect input from many quarters.

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

Utilizing buprenorphine-naloxone to treat illicit and prescription-opioid dependence. [2022] To review current evidence on buprenorphine-naloxone (bup/nx) for the treatment of opioid-use disorders, with a focus on strategies for clinical management and office-based patient care.

6. Ireland pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. [2021] Sublingual formulations of buprenorphine (BUP) and BUP/naloxone have well-established pharmacokinetic and pharmacodynamic profiles, and are safe and effective for treating opioid use disorder. Since approvals of these formulations, their clinical use has increased. Yet, questions have arisen as to how BUP binding to mu-opioid receptors (μORs), the neurobiological target for this medication, relate to its clinical application. BUP produces dose- and time-related alterations of μOR availability but some clinicians express concern about whether doses higher than those needed to prevent opioid withdrawal symptoms are warranted, and policymakers consider limiting reimbursement for certain BUP dosing regimens.

7. France pubmed.ncbi.nlm.nih.gov

Prolonged-release buprenorphine formulations: Perspectives for clinical practice. [2021] Buprenorphine and methadone are the two main opioid agonist treatments approved for opioid use disorder. Buprenorphine is a partial agonist of the mu opioid receptors, which has been merely available through sublingual form until now. In practice, the use of buprenorphine is smoother than that of methadone, and it induces reduced risks of overdose. However, sublingual buprenorphine also exposes to risks (e.g., withdrawal, misuse) and constraints (e.g., daily intake). Three new galenic formulations of prolonged-release buprenorphine (PRB) are being commercialized and should allow some improvements in patients' comfort and safety. This narrative review aims to describe the main technical features and efficacy and safety data of these PRBs, as well as patients' and professionals' expectancies and concerns, using data of the scientific literature and the regulatory texts. PRBs consist of one subcutaneous implant and two subcutaneous injection depots. Sixmo®/Probuphine® is a six-month-long implant which needs to be surgically placed and removed and is approved for subjects previously treated with a maximum daily dose of 8mg of sublingual buprenorphine, and can be used only for two successive periods of six months before the subject needs to be switched back to sublingual form. Sublocade® is a one-month-long depot formulation that is indicated in switch from sublingual buprenorphine, and which proposes only two dose schemes, i.e., 100 and 300mg monthly. Buvidal®/Brixadi® is a one-week- or one-month-long depot formulation with multiple dosages, which can be used in initiation or in switched from sublingual formulations. While opioid users report some concerns with a risk of coercive use of long-acting forms of buprenorphine, both users and professionals deem that these new specialties could be particularly appreciated in stabilized patients bothered with the daily intake of the treatments, or specific situations at risk of treatment dropout (e.g., following hospital discharge or prison release).

8. France pubmed.ncbi.nlm.nih.gov

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. [2022] Buprenorphine and methadone are the two main opioids agonist treatments approved for opioid use disorder. Buprenorphine is a partial agonist of the mu-opioid receptors, which has been merely available through sublingual form until now. In practice, the use of buprenorphine is smoother than that of methadone, and it induces reduced risks of overdose. However, sublingual buprenorphine also exposes to risks (e.g., withdrawal, misuse) and constraints (e.g., daily intake). Three new galenic formulations of prolonged-release buprenorphine (PRB) are being commercialized and should allow some improvements in patients' comfort and safety. This narrative review aims to describe the main technical features and efficacy and safety data of these PRBs, as well as patients' and professionals' expectancies and concerns, using data of the scientific literature and the regulatory texts. PRBs consist of one subcutaneous implant and two subcutaneous injection depots. Sixmo®/Probuphine® is a six-month-long implant which needs to be surgically placed and removed and is approved for subjects previously treated with a maximum daily dose of 8mg of sublingual buprenorphine, and can be used only for two successive periods of six months before the subject needs to be switched back to sublingual form. Sublocade® is a one-month-long depot formulation that is indicated in switch from sublingual buprenorphine, and which proposes only two dose schemes, i.e., 100 and 300mg monthly. Buvidal®/Brixadi® is a one-week- or one-month-long depot formulation with multiple dosages, which can be used in initiation or in switched from sublingual formulations. While opioid users report some concerns with a risk of coercive use of long-acting forms of buprenorphine, both users and professionals deem that these new specialties could be particularly appreciated in stabilized patients bothered with the daily intake of the treatments, or specific situations at risk of treatment dropout (e.g., following hospital discharge or prison release).

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

Buprenorphine Treatment for Opioid Use Disorder: An Overview. [2022] Opioid use disorder affects over 26 million individuals worldwide. There are currently three World Health Organization-recommended and US Food and Drug Administration-approved medication treatments for opioid use disorder: the full opioid agonist methadone, the opioid partial agonist buprenorphine, and the opioid receptor antagonist naltrexone. We provide a review of the use of buprenorphine for the treatment of opioid use disorder and discuss the barriers, challenges, risks, and efficacy of buprenorphine treatment vs. other treatments. Although evidence from numerous studies has shown buprenorphine to be effective for the treatment of opioid use disorder, a majority of patients with opioid use disorder do not receive buprenorphine, or any other medical treatment. We review the different formulations of buprenorphine, including newer long-acting injectable formulations that may decrease the risk of diversion and improve adherence.

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

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment. [2021] Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients' demographic and clinical characteristics were associated with better response to one medication or the other.