Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (RDD)

NCT ID: NCT04464980

Last Updated: 2025-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

1516 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-08

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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The main objectives of this study are:

1. To test strategies to improve retention in treatment on medications for opioid use disorder (MOUD), among patients initiating treatment for OUD.
2. To test strategies to improve outcomes among patients who have achieved stable remission on MOUD and want to discontinue MOUD.
3. To develop models to predict who is able to discontinue MOUD without relapse, based on patient characteristics, including duration of MOUD prior to discontinuation.

The study will have a multicenter, randomized, pragmatic non-blinded design. The study has two phases, a Retention Phase and a Discontinuation Phase.

Conditions

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Opioid Use Disorder (OUD)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Retention Phase: 3x2 for BUP; 1x2 for XR-NTX; Discontinuation Phase: 2x2 for SL-BUP; 1x2 for XR-BUP; 1x2 for XR-NTX
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Retention: SL-BUP standard dose + MM

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 Type EXPERIMENTAL

SL-BUP

Intervention Type DRUG

Daily dosing of sublingual buprenorphine-naloxone

MM

Intervention Type BEHAVIORAL

MM consists of standard Medical Management and the usual counseling at the treatment program.

Retention: SL-BUP high dose + MM

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 Type EXPERIMENTAL

SL-BUP

Intervention Type DRUG

Daily dosing of sublingual buprenorphine-naloxone

MM

Intervention Type BEHAVIORAL

MM consists of standard Medical Management and the usual counseling at the treatment program.

Retention: XR-BUP + MM

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

Group Type EXPERIMENTAL

XR-BUP

Intervention Type DRUG

Weekly/monthly dosing of extended-release injectable buprenorphine

MM

Intervention Type BEHAVIORAL

MM consists of standard Medical Management and the usual counseling at the treatment program.

Retention: XR-NTX + MM

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

Group Type EXPERIMENTAL

XR-NTX

Intervention Type DRUG

Monthly dosing of extended-release injectable naltrexone

MM

Intervention Type BEHAVIORAL

MM consists of standard Medical Management and the usual counseling at the treatment program.

Retention: SL-BUP standard dose + MMR

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 Type EXPERIMENTAL

SL-BUP

Intervention Type DRUG

Daily dosing of sublingual buprenorphine-naloxone

MMR

Intervention Type BEHAVIORAL

MMR consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Retention: SL-BUP high dose + MMR

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 Type EXPERIMENTAL

SL-BUP

Intervention Type DRUG

Daily dosing of sublingual buprenorphine-naloxone

MMR

Intervention Type BEHAVIORAL

MMR consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Retention: XR-BUP + MMR

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

Group Type EXPERIMENTAL

XR-BUP

Intervention Type DRUG

Weekly/monthly dosing of extended-release injectable buprenorphine

MMR

Intervention Type BEHAVIORAL

MMR consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Retention: XR-NTX + MMR

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

Group Type EXPERIMENTAL

XR-NTX

Intervention Type DRUG

Monthly dosing of extended-release injectable naltrexone

MMR

Intervention Type BEHAVIORAL

MMR consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Discontinuation: Discontinue SL-BUP with SL-BUP + MM

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

Group Type EXPERIMENTAL

SL-BUP

Intervention Type DRUG

Daily dosing of sublingual buprenorphine-naloxone

MM

Intervention Type BEHAVIORAL

MM consists of standard Medical Management and the usual counseling at the treatment program.

Discontinuation: Discontinue SL-BUP with XR-BUP + MM

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

Group Type EXPERIMENTAL

XR-BUP

Intervention Type DRUG

Weekly/monthly dosing of extended-release injectable buprenorphine

MM

Intervention Type BEHAVIORAL

MM consists of standard Medical Management and the usual counseling at the treatment program.

Discontinuation: Discontinue XR-BUP with XR-BUP + MM

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

Group Type EXPERIMENTAL

XR-BUP

Intervention Type DRUG

Weekly/monthly dosing of extended-release injectable buprenorphine

MM

Intervention Type BEHAVIORAL

MM consists of standard Medical Management and the usual counseling at the treatment program.

Discontinuation: Discontinue XR-NTX with XR-NTX + MM

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

Group Type EXPERIMENTAL

XR-NTX

Intervention Type DRUG

Monthly dosing of extended-release injectable naltrexone

MM

Intervention Type BEHAVIORAL

MM consists of standard Medical Management and the usual counseling at the treatment program.

Discontinuation: Discontinue SL-BUP with SL-BUP + MMD

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 Type EXPERIMENTAL

SL-BUP

Intervention Type DRUG

Daily dosing of sublingual buprenorphine-naloxone

MMD

Intervention Type BEHAVIORAL

MMD consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Discontinuation: Discontinue SL-BUP with XR-BUP + MMD

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 Type EXPERIMENTAL

XR-BUP

Intervention Type DRUG

Weekly/monthly dosing of extended-release injectable buprenorphine

MMD

Intervention Type BEHAVIORAL

MMD consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Discontinuation: Discontinue XR-BUP with XR-BUP + MMD

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 Type EXPERIMENTAL

XR-BUP

Intervention Type DRUG

Weekly/monthly dosing of extended-release injectable buprenorphine

MMD

Intervention Type BEHAVIORAL

MMD consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Discontinuation: Discontinue XR-NTX with XR-NTX + MMD

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 Type EXPERIMENTAL

XR-NTX

Intervention Type DRUG

Monthly dosing of extended-release injectable naltrexone

MMD

Intervention Type BEHAVIORAL

MMD consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Interventions

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SL-BUP

Daily dosing of sublingual buprenorphine-naloxone

Intervention Type DRUG

XR-BUP

Weekly/monthly dosing of extended-release injectable buprenorphine

Intervention Type DRUG

XR-NTX

Monthly dosing of extended-release injectable naltrexone

Intervention Type DRUG

MM

MM consists of standard Medical Management and the usual counseling at the treatment program.

Intervention Type BEHAVIORAL

MMR

MMR consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Intervention Type BEHAVIORAL

MMD

MMD consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Intervention Type BEHAVIORAL

Other Intervention Names

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sublingual buprenorphine Suboxone extended-release buprenorphine CAM2038 Brixadi extended-release naltrexone Vivitrol

Eligibility Criteria

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Inclusion Criteria

1. 18 years of age or older;
2. Meet DSM-5 criteria for current opioid use disorder (heroin, fentanyl or other synthetic opioids, and/or prescription opioids);
3. Seeking treatment for opioid use disorder and choosing either buprenorphine (BUP) or extended-release injection naltrexone (XR-NTX);
4. If choosing buprenorphine, willing to be randomized to SL-BUP-16mg, SL-BUP-32mg, or XR-BUP;
5. Willing to be randomized to either MM (standard Medical Management plus counseling treatment as usual available at the site) or MMR (MM plus usual counseling and access to an app delivering CM + CBT);
6. 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;
7. Willing and able to provide written informed consent;
8. Able to speak English sufficiently to understand the study procedures;
9. If female of childbearing potential, willing to practice an effective method of birth control for the duration of participation in the study (participants who become pregnant during the study will continue to be followed; treatment may be modified consistent with pregnancy).


1. 18 years of age or older;
2. Have been receiving buprenorphine for OUD for at least the past year or XR-NTX pharmacotherapy for OUD for at least the past 6 months prior to consent for the Discontinuation Phase;
3. Express the desire to discontinue MOUD after a shared decision-making discussion with the treating provider;
4. Meet stability criteria, i.e., have abstained from opioids (other than buprenorphine), cocaine, methamphetamine, and non-prescribed benzodiazepines for the past ≥12 weeks, and do not meet DSM-5 criteria for current (≥12 weeks) alcohol use disorder (participants with cannabis use will be eligible);
5. If currently taking buprenorphine, are willing to take either SL-BUP or XR-BUP if randomized to that condition;
6. Willing to be randomized to either MM or to MMD;
7. Able to provide written informed consent after discussion with their provider regarding the risks of discontinuation;
8. Able to speak English sufficiently to understand the study procedures;
9. If female of childbearing potential, willing to practice an effective method of birth control while in the study and taking study medication (participants who become pregnant during the study will continue to be followed; treatment may be modified consistent with pregnancy).

Exclusion Criteria

1. 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:

1. 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;
2. 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);
3. Current severe alcohol, benzodiazepine, or other depressant or sedative hypnotic use, requiring a different level of care (e.g., hospitalization);
2. Suicidal or homicidal ideation or behavior requiring a different level of care (e.g., hospitalization);
3. Known allergy or sensitivity to preferred medication or its components;
4. Maintenance on methadone at the time of signing consent;
5. For those preferring XR-NTX, presence of pain of sufficient severity as to require ongoing pain management with opioids;
6. 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);
7. If female, currently pregnant or breastfeeding or planning on conception;
8. 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;
9. Have used the reSET-O or CHESS Connections mHealth apps in the 3 months prior to consent;
10. Other major reasons that might prevent an individual from participating in the study (e.g., a planned move out of the area).


1. 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:

1. 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;
2. 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);
2. Suicidal or homicidal ideation or behavior requiring a different level of care (e.g., hospitalization);
3. For participants entering the study taking buprenorphine, presence of pain requiring or likely requiring ongoing pain management with buprenorphine or other opioids;
4. If female, currently pregnant or breastfeeding or planning on conception;
5. Use of opioids (other than buprenorphine), cocaine, methamphetamine, or non-prescribed benzodiazepines in the past 12 weeks;
6. Meets current DSM-5 criteria for any current alcohol use disorder;
7. 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;
8. Have used the Connections mHealth app in the 3 months prior to consent (other than Connections in the Retention Phase);
9. Other major reasons that might prevent an individual from participating in the study (e.g., a planned move out of the area.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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New York State Psychiatric Institute

OTHER

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role collaborator

Mclean Hospital

OTHER

Sponsor Role collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

NYU Langone Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Edward V Nunes, MD

Role: PRINCIPAL_INVESTIGATOR

New York State Psychiatric Institute/Columbia University Irving Medical Center

John Rotrosen, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Roger Weiss, MD

Role: PRINCIPAL_INVESTIGATOR

Harvard Medical School/McLean Hospital

Locations

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University of Arkansas for Medical Sciences (UAMS) / Center for Addiction Services and Treatment (CAST)

Little Rock, Arkansas, United States

Site Status

Tarzana Treatment Centers, Inc.

Tarzana, California, United States

Site Status

Liberation Programs, Inc.

Bridgeport, Connecticut, United States

Site Status

Operation PAR

Clearwater, Florida, United States

Site Status

Gateway Community Services

Jacksonville, Florida, United States

Site Status

Aspire Health Partners

Orlando, Florida, United States

Site Status

Mountain Manor / Maryland Treatment Centers

Baltimore, Maryland, United States

Site Status

McLean Hospital

Belmont, Massachusetts, United States

Site Status

Stanley Street Treatment and Resources, Inc.

Fall River, Massachusetts, United States

Site Status

Square Medical Group, LLC

Newton, Massachusetts, United States

Site Status

Gibson Center for Behavioral Change

Cape Girardeau, Missouri, United States

Site Status

Dartmouth Hitchcock - ATP

Lebanon, New Hampshire, United States

Site Status

University of New Mexico Addiction and Substance Abuse Program

Albuquerque, New Mexico, United States

Site Status

Bellevue Hospital Center

New York, New York, United States

Site Status

Adapt Integrated Health Care

Roseburg, Oregon, United States

Site Status

Adapt Integrated Health Care

Winston, Oregon, United States

Site Status

Center for Psychiatric and Chemical Dependency Services (CPCDS)

Pittsburgh, Pennsylvania, United States

Site Status

Internal Medicine Recovery Engagement Program (IM-REP)

Pittsburgh, Pennsylvania, United States

Site Status

Shoreline Behavioral Health Services

Conway, South Carolina, United States

Site Status

Huntsman Mental Health Institute / University of Utah

Salt Lake City, Utah, United States

Site Status

Chestnut Ridge Center

Morgantown, West Virginia, United States

Site Status

Countries

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United States

References

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Shulman M, Meyers-Ohki S, Novo P, Provost S, Ohrtman K, Van Veldhuisen P, Oden N, Otterstatter M, Bailey GL, Liu D, Rotrosen J, Weiss RD, Nunes EV. Optimizing retention strategies for opioid use disorder pharmacotherapy: The retention phase of the CTN-0100 trial (RDD). Contemp Clin Trials. 2025 Mar;150:107816. doi: 10.1016/j.cct.2025.107816. Epub 2025 Jan 20.

Reference Type DERIVED
PMID: 39842691 (View on PubMed)

Shulman M, Provost S, Ohrtman K, Novo P, Meyers-Ohki S, Van Veldhuisen P, Oden N, Otterstatter M, Bailey GL, Liu D, Rotrosen J, Nunes EV, Weiss RD. Discontinuation of medication treatment for opioid use disorder after a successful course: The discontinuation phase of the CTN-0100 (RDD) trial. Contemp Clin Trials. 2024 Jul;142:107543. doi: 10.1016/j.cct.2024.107543. Epub 2024 Apr 23.

Reference Type DERIVED
PMID: 38657730 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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CTN-0100

Identifier Type: OTHER

Identifier Source: secondary_id

UG1DA013035

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1DA015831

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20-PRS-057

Identifier Type: OTHER

Identifier Source: secondary_id

146193

Identifier Type: OTHER

Identifier Source: secondary_id

19-01363

Identifier Type: -

Identifier Source: org_study_id

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