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Opioid Use Disorder (OUD)Phase 2NCT04464980

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

A Phase 2 study testing SL-BUP, XR-BUP and XR-NTX in people with Opioid Use Disorder (OUD), run by NYU Langone Health at 21 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Opioid Use Disorder (OUD)
What is being tested?
SL-BUP, XR-BUP and XR-NTX
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,516 participants
Where
21 sitesUnited States
Study dates
8 Jun 2021to 31 Jan 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 years of age or older;
  • Meet DSM-5 criteria for current opioid use disorder (heroin, fentanyl or other synthetic opioids, and/or prescription opioids);
  • Seeking treatment for opioid use disorder and choosing either buprenorphine (BUP) or extended-release injection naltrexone (XR-NTX);
  • If choosing buprenorphine, willing to be randomized to SL-BUP-16mg, SL-BUP-32mg, or XR-BUP;
  • 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);
  • 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;
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  • Willing and able to provide written informed consent;
  • Able to speak English sufficiently to understand the study procedures;
  • 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).
  • 18 years of age or older;
  • 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;
  • Express the desire to discontinue MOUD after a shared decision-making discussion with the treating provider;
  • 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);
  • If currently taking buprenorphine, are willing to take either SL-BUP or XR-BUP if randomized to that condition;
  • Willing to be randomized to either MM or to MMD;
  • Able to provide written informed consent after discussion with their provider regarding the risks of discontinuation;
  • Able to speak English sufficiently to understand the study procedures;
  • 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).

Who cannot join

  • 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;
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  • 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-O or CHESS Connections 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 than Connections in the Retention Phase);
  • Other major reasons that might prevent an individual from participating in the study (e.g., a planned move out of the area.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites

  • University of New Mexico Addiction and Substance Abuse Program

    Albuquerque, New Mexico, 87106

  • Mountain Manor / Maryland Treatment Centers

    Baltimore, Maryland, 21229

  • McLean Hospital

    Belmont, Massachusetts, 02478

  • Liberation Programs, Inc.

    Bridgeport, Connecticut, 06610

  • Gibson Center for Behavioral Change

    Cape Girardeau, Missouri, 63703

  • Operation PAR

    Clearwater, Florida, 33760

  • Shoreline Behavioral Health Services

    Conway, South Carolina, 29526

  • Stanley Street Treatment and Resources, Inc.

    Fall River, Massachusetts, 02720

  • Gateway Community Services

    Jacksonville, Florida, 32204

  • Dartmouth Hitchcock - ATP

    Lebanon, New Hampshire, 03766

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

    Little Rock, Arkansas, 72205

  • Chestnut Ridge Center

    Morgantown, West Virginia, 26505

  • Bellevue Hospital Center

    New York, New York, 10016

  • Square Medical Group, LLC

    Newton, Massachusetts, 02458

  • Aspire Health Partners

    Orlando, Florida, 32806

  • Center for Psychiatric and Chemical Dependency Services (CPCDS)

    Pittsburgh, Pennsylvania, 15213

  • Internal Medicine Recovery Engagement Program (IM-REP)

    Pittsburgh, Pennsylvania, 15219

  • Adapt Integrated Health Care

    Roseburg, Oregon, 97470

  • Huntsman Mental Health Institute / University of Utah

    Salt Lake City, Utah, 84108

  • Tarzana Treatment Centers, Inc.

    Tarzana, California, 91356

  • Adapt Integrated Health Care

    Winston, Oregon, 97496

Other trials in United States

About this study

Official title: NIDA-CTN-0100: Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (RDD)

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.

Read the detailed description

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.

Being tested
SL-BUP, XR-BUP, XR-NTX, MM, MMR
Medical subject headings
Opioid-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SL-BUPDrug

    Also called sublingual buprenorphine, Suboxone

    Daily dosing of sublingual buprenorphine-naloxone

  • XR-BUPDrug

    Also called extended-release buprenorphine, CAM2038, Brixadi

    Weekly/monthly dosing of extended-release injectable buprenorphine

  • XR-NTXDrug

    Also called extended-release naltrexone, Vivitrol

    Monthly dosing of extended-release injectable naltrexone

  • MMBehavioural

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

  • MMRBehavioural

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

  • MMDBehavioural

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

Study groups in NCT04464980
Study groupRoleWhat they receive
Retention: SL-BUP standard dose + MMExperimentalStandard dose sublingual buprenorphine-naloxone (SL-BUP) 16mg/day target plus MM, consisting of standard Medical Management and usual counseling at the treatment program.
Receives: Drug: SL-BUP; Behavioral: MM
Retention: SL-BUP high dose + MMExperimentalHigh dose sublingual buprenorphine-naloxone (SL-BUP) 32mg/day target plus MM, consisting of standard Medical Management and usual counseling at the treatment program.
Receives: Drug: SL-BUP; Behavioral: MM
Retention: XR-BUP + MMExperimentalExtended-release injectable buprenorphine (XR-BUP) plus MM, consisting of standard Medical Management and usual counseling at the treatment program.
Receives: Drug: XR-BUP; Behavioral: MM
Retention: XR-NTX + MMExperimentalExtended-release injectable naltrexone (XR-NTX) plus MM, consisting of standard Medical Management and usual counseling at the treatment program.
Receives: Drug: XR-NTX; Behavioral: MM
Retention: SL-BUP standard dose + MMRExperimentalStandard dose sublingual buprenorphine-naloxone (SL-BUP) 16mg/day target plus MMR, consisting of Medical Management and usual counseling, plus a technology-based behavioral component.
Receives: Drug: SL-BUP; Behavioral: MMR
Retention: SL-BUP high dose + MMRExperimentalHigh 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.
Receives: Drug: SL-BUP; Behavioral: MMR
Retention: XR-BUP + MMRExperimentalExtended-release injectable buprenorphine (XR-BUP) plus MMR, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.
Receives: Drug: XR-BUP; Behavioral: MMR
Retention: XR-NTX + MMRExperimentalExtended-release injectable naltrexone (XR-NTX) plus MMR, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.
Receives: Drug: XR-NTX; Behavioral: MMR
Discontinuation: Discontinue SL-BUP with SL-BUP + MMExperimentalStart on SL-BUP, taper with SL-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.
Receives: Drug: SL-BUP; Behavioral: MM
Discontinuation: Discontinue SL-BUP with XR-BUP + MMExperimentalStart on SL-BUP, taper with XR-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.
Receives: Drug: XR-BUP; Behavioral: MM
Discontinuation: Discontinue XR-BUP with XR-BUP + MMExperimentalStart on XR-BUP, taper with XR-BUP, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.
Receives: Drug: XR-BUP; Behavioral: MM
Discontinuation: Discontinue XR-NTX with XR-NTX + MMExperimentalStart on XR-NTX, taper with XR-NTX, plus MM, consisting of standard Medical Management and usual counseling at the treatment program.
Receives: Drug: XR-NTX; Behavioral: MM
Discontinuation: Discontinue SL-BUP with SL-BUP + MMDExperimentalStart on SL-BUP, taper with SL-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.
Receives: Drug: SL-BUP; Behavioral: MMD
Discontinuation: Discontinue SL-BUP with XR-BUP + MMDExperimentalStart on SL-BUP, taper with XR-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.
Receives: Drug: XR-BUP; Behavioral: MMD
Discontinuation: Discontinue XR-BUP with XR-BUP + MMDExperimentalStart on XR-BUP, taper with XR-BUP, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.
Receives: Drug: XR-BUP; Behavioral: MMD
Discontinuation: Discontinue XR-NTX with XR-NTX + MMDExperimentalStart on XR-NTX, taper with XR-NTX, plus MMD, consisting of standard Medical Management and usual counseling, plus a technology-based behavioral component.
Receives: Drug: XR-NTX; Behavioral: MMD

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Retention: Continuous retention in MOUD treatment through 26 weeks

    Binary (yes/no). Continuously enrolled in maintenance treatment on one or more of the evidence-based MOUD modalities (e.g., SL-BUP, XR-BUP, XR-NTX, or methadone maintenance) with no more than a 28-day gap on MOUD over the 26-week period.

    Measured: Retention: from randomization through week 26

  2. Discontinuation: Completed Discontinuation without Relapse

    Binary (yes/no). Discontinuing MOUD during the taper period, no return to MOUD, and no relapse to opioid use, either during the taper (up to 48 weeks for those entering on BUP or 24 weeks for those entering on XR-NTX) or during the 24 weeks after MOUD is discontinued.

    Measured: Discontinuation: from randomization through week 24 follow up

Secondary outcomes (7)

  1. Retention KS1: Weekly opioid abstinence

    Weekly opioid abstinence (measured by Timeline Followback, not contradicted by toxicology test). Repeated yes/no measure for each of weeks 1 through 26.

    Measured: Retention: from randomization through week 26

  2. Retention KS2: Treatment effectiveness

    Retention treatment effectiveness, measured by the Treatment Effectiveness Assessment (TEA, Ling et. al, 2012); a brief instrument to assess patient progress in treatment and recovery along 4 domains (substance use, health, lifestyle and community) at week 26.

    Measured: Retention: at week 26

  3. Retention KS3: Treatment by baseline severity

    Treatment by baseline severity interaction where severity is indicated by the randomization stratum injection use (yes/no).

    Measured: Retention: at week 26

  4. Discontinuation KS1: Completed Discontinuation

    Completed Discontinuation without regard to relapse status

    Measured: Discontinuation: from randomization through week 24 follow up

  5. Discontinuation KS2: Relapse

    Relapse - separate binary outcome without regard to discontinuation status

    Measured: Discontinuation: from randomization through week 24 follow up

  6. Discontinuation KS3: Safety

    Safety outcomes (binary, any one or more occurrences): overdoses, all non-fatal plus fatal.

    Measured: Discontinuation: from randomization through week 24 follow up

  7. Discontinuation KS4: Treatment effectiveness

    Discontinuation treatment effectiveness, measured by the Treatment Effectiveness Assessment (TEA, Ling et. al, 2012); a brief instrument to assess patient progress in treatment and recovery along 4 domains (substance use, health, lifestyle and community) at week 24. Measured at the end of taper (EOT): up to 24 weeks for tapers with XR-NTX and up to 48 weeks for tapers with BUP; and at the week 24 follow up (primary outcome timepoint).

    Measured: Discontinuation: at end of taper (EoT) and week 24 follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2020
  2. Study start8 Jun 2021
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
Retention Phase: 3x2 for BUP; 1x2 for XR-NTX; Discontinuation Phase: 2x2 for SL-BUP; 1x2 for XR-BUP; 1x2 for XR-NTX
Masking
None (open label)
Enrolment
1,516 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04464980
Sponsor's protocol ID
19-01363
Other IDs
CTN-0100, UG1DA013035, UG1DA015831, 20-PRS-057, 146193
Status last verified
Jul 2026
First submitted
29 Jun 2020
Last updated
1 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: This study will comply with the NIH Data Sharing Policy and Implementation Guidance (https://grants.nih.gov/grants/policy/data\_sharing/data\_sharing\_guidance.htm) and (for HEAL-funded studies) the HEAL Public Access and Data Sharing Policy (https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/research/heal-public-access-data-sharing-policy). Primary data for this study will be available to the public in the NIDA data repository. For more details on data sharing please visit https://datashare.nida.nih.gov/. The primary outcome(s) publication will be included along with study underlying primary data in the data share repository, and it will also be deposited in PubMed Central http://www.pubmedcentral.nih.gov/ per NIH Policy (http://publicaccess.nih.gov/).

Publications

  • 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.

    PubMed 39842691

  • 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.

    PubMed 38657730

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SL-BUP, XR-BUP and XR-NTX in people with Opioid Use Disorder (OUD), run by NYU Langone Health at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Retention: Continuous retention in MOUD treatment through 26 weeks (time frame: Retention: from randomization through week 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04464980, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.

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