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

Opioid Use Disorder (OUD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04464980
• Other study ID #: 19-01363
• Secondary ID: CTN-0100UG1DA013
• Status: Recruiting
• Phase: Phase 2
• Start date: June 8, 2021
• Est. completion date: December 30, 2026

Study information

• Verified date: June 2024
• Source: NYU Langone Health
• Contact: Project Manager
• Phone: 646-754-4786
• Email: RDD[@]nyulangone.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2190
• Est. completion date: December 30, 2026
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria for Retention Phase:

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).

Exclusion Criteria for Retention Phase:

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).

Inclusion Criteria for Discontinuation Phase:

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 for Discontinuation Phase:

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.

Related Conditions & MeSH terms

• Opioid Use Disorder (OUD)
• Opioid-Related Disorders
• Substance-Related Disorders

Intervention

Drug:
• SL-BUP
Daily dosing of sublingual buprenorphine-naloxone
• XR-BUP
Weekly/monthly dosing of extended-release injectable buprenorphine
• XR-NTX
Monthly dosing of extended-release injectable naltrexone

Behavioral:
• MM
MM consists of standard Medical Management and the usual counseling at the treatment program.
• MMR
MMR consists of Medical Management and usual counseling, plus a technology-based behavioral component.
• MMD
MMD consists of Medical Management and usual counseling, plus a technology-based behavioral component.

Locations

Country	Name	City	State
United States	University of New Mexico Addiction and Substance Abuse Program	Albuquerque	New Mexico
United States	Mountain Manor / Maryland Treatment Centers	Baltimore	Maryland
United States	McLean Hospital	Belmont	Massachusetts
United States	Liberation Programs, Inc.	Bridgeport	Connecticut
United States	Gibson Center for Behavioral Change	Cape Girardeau	Missouri
United States	Operation PAR	Clearwater	Florida
United States	Shoreline Behavioral Health Services	Conway	South Carolina
United States	Stanley Street Treatment and Resources, Inc.	Fall River	Massachusetts
United States	Gateway Community Services	Jacksonville	Florida
United States	Dartmouth Hitchcock - ATP	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences (UAMS) / Center for Addiction Services and Treatment (CAST)	Little Rock	Arkansas
United States	Chestnut Ridge Center	Morgantown	West Virginia
United States	Bellevue Hospital Center	New York	New York
United States	Square Medical Group, LLC	Newton	Massachusetts
United States	Aspire Health Partners	Orlando	Florida
United States	Center for Psychiatric and Chemical Dependency Services (CPCDS)	Pittsburgh	Pennsylvania
United States	Internal Medicine Recovery Engagement Program (IM-REP)	Pittsburgh	Pennsylvania
United States	Adapt Integrated Health Care	Roseburg	Oregon
United States	Huntsman Mental Health Institute / University of Utah	Salt Lake City	Utah
United States	Tarzana Treatment Centers, Inc.	Tarzana	California
United States	Adapt Integrated Health Care	Winston	Oregon

Sponsors (7)

Lead Sponsor	Collaborator
NYU Langone Health	Columbia University, Harvard Medical School (HMS and HSDM), Mclean Hospital, National Institute on Drug Abuse (NIDA), New York State Psychiatric Institute, The Emmes Company, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	R-Other 1a: Continuous opioid abstinence-weeks 23-26	Binary indicator of continuous abstinence from opioids in weeks 23 to 26 (measured by Timeline Followback, not contradicted by toxicology test)	Retention: weeks 23-26
Other	R-Other 1b: Continuous opioid abstinence-weeks 47-50	Binary indicator of continuous abstinence from opioids in weeks 47 to 50 (measured by Timeline Followback, not contradicted by toxicology test)	Retention: weeks 47-50
Other	R-Other 1c: Continuous opioid abstinence-weeks 71-74	Binary indicator of continuous abstinence from opioids in weeks 71 to 74 (measured by Timeline Followback, not contradicted by toxicology test)	Retention: weeks 71-74
Other	R-Other 2: Weekly opioid abstinence	Weekly opioid abstinence (measured by Timeline Followback, not contradicted by toxicology test). Repeated yes/no measure for each of weeks 27 through 74.	Retention: weeks 27-74
Other	R-Other 3: Weekly abstinence from other substance use	Weekly abstinence from other substance use (measured by Timeline Followback, not contradicted by toxicology test)	Retention: weeks 0-74
Other	R-Other 4: Craving	Craving, measured by the Opioid Craving Scale	Retention: weeks 0-98
Other	R-Other 5a: Stable abstinence at week 26	Stable abstinence, as defined by the same stability criteria as in the Discontinuation Phase (point prevalence stability at week 26), i.e., past =12 weeks of consecutive abstinence from opioids (other than prescribed buprenorphine), methamphetamine, and cocaine, no non-prescribed benzodiazepine use, and no current (=12 weeks) alcohol use disorder (any severity); measured by Timeline Followback, not contradicted by toxicology test (both repeated measures), and DSM-5 checklist for current alcohol use disorder (which is performed only when these abstinence criteria are met)	Retention: week 26
Other	R-Other 5b: Stable abstinence at week 50	Stable abstinence, as defined by the same stability criteria as in the Discontinuation Phase (point prevalence stability at week 50), i.e., past =12 weeks of consecutive abstinence from opioids (other than prescribed buprenorphine), methamphetamine, and cocaine, no non-prescribed benzodiazepine use, and no current (=12 weeks) alcohol use disorder (any severity); measured by Timeline Followback, not contradicted by toxicology test (both repeated measures), and DSM-5 checklist for current alcohol use disorder (which is performed only when these abstinence criteria are met)	Retention: week 50
Other	R-Other 5c: Stable abstinence at week 74	Stable abstinence, as defined by the same stability criteria as in the Discontinuation Phase (point prevalence stability at week 74), i.e., past =12 weeks of consecutive abstinence from opioids (other than prescribed buprenorphine), methamphetamine, and cocaine, no non-prescribed benzodiazepine use, and no current (=12 weeks) alcohol use disorder (any severity); measured by Timeline Followback, not contradicted by toxicology test (both repeated measures), and DSM-5 checklist for current alcohol use disorder (which is performed only when these abstinence criteria are met)	Retention: week 74
Other	R-Other 6: Retention in MOUD at week 50	Point prevalence of retention in MOUD treatment (defined as no gap of 28 days or more in MOUD) at 50 weeks after date of randomization (binary, measured by Timeline Followback)	Retention: week 50
Other	R-Other 7: Retention in MOUD at week 74	Point prevalence of retention in MOUD treatment at 74 weeks after date of randomization, measured by TLFB	Retention: week 74
Other	R-Other 8: Dropout from MOUD treatment	Dropout from MOUD treatment (time to event), i.e., a gap of 28 or more days in MOUD, event to have started at the beginning of the 28-day gap (measured by Timeline Followback)	Retention: weeks 0-74
Other	R-Other 9: Depression	Depression (measured by the Patient Health Questionnaire (PHQ) 9) over the first 26 weeks	Retention: weeks 0-26
Other	R-Other 10: Anxiety	Anxiety, measured by the measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Preference (PROPr) over the first 26 weeks	Retention: weeks 0-26
Other	R-Other 11: Stress	Stress, measured by the Perceived Stress Scale, over the first 26 weeks	Retention: weeks 0-26
Other	R-Other 12: Pain	Pain, measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Preference (PROPr), over the first 26 weeks	Retention: weeks 0-26
Other	R-Other 13: Recovery capital	Recovery capital, measured by the Brief Assessment of Recovery Capital (BARC) 10 item scale, over the first 26 weeks	Retention: weeks 0-26
Other	R-Other 14: Negative consequences of opioid use	Negative consequences of opioid use, measured by the Short Inventory of Problems-Revised, over the first 26 weeks	Retention: weeks 0-26
Other	R-Other 15: Sexual risk	Sexual risk, measured by two questions regarding sexual behavior, over the first 26 weeks	Retention: weeks 0-26
Other	R-Other 16: Rate of incarceration	Rate of incarcerations, collected on the Non-Medical and Other Services form, over the first 26 weeks	Retention: weeks 0-26
Other	R-Other 17: Rate of homelessness	Rate of homelessness, collected on the Study Demographics form, over the first 26 weeks	Retention: weeks 0-26
Other	D-Other 1: Relapse	Relapse (time to event): defined as self-reported opioid use on more than 4 days in any consecutive 28-day period (event to begin on the first day of use), or 2 or more consecutive opioid-positive drug tests (event to begin with the first opioid-positive test) or any self-reported injection drug use (whichever comes first).	Discontinuation: during taper and through week 24 follow up
Other	D-Other 2: Withdrawal symptoms	Withdrawal symptoms, measured by Subjective Opioid Withdrawal Scale (SOWS), during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 3: Craving	Craving, measured by the Opioid Craving Scale, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 4: Depression	Depression, measured by the Patient Health Questionnaire (PHQ) 9 item, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 5: Anxiety	Anxiety, measured by the measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Preference (PROPr), during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 6: Stress	Stress, measured by the Perceived Stress Scale, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 7: Pain	Pain, measured by the measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Preference (PROPr), during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 8a: Recovery capital (BARC-10)	Recovery capital, measured by the Brief Assessment of Recovery Capital (BARC) 10 item scale, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 8b: Recovery capital (RCS)	Recovery capital, measured by the Recovery Capital Scale; six additional questions more specific to participants with OUD, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 9: Negative consequences of opioid use	Negative consequences of opioid use, measured by the Short Inventory of Problems-Revised, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 10: Sexual risk	Sexual risk, measured by two questions regarding sexual behavior, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 11: Rate of incarceration	Incarcerations, collected on the Non-Medical and Other Services form, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Other	D-Other 12: Rate of homelessness	Homelessness, collected on the Study Demographics form, during taper and follow up	Discontinuation: during taper and through week 24 follow up
Primary	Retention: Continuous retention in MOUD treatment at 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 in MOUD over the 26-week period.	Retention: at week 26
Primary	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.	Discontinuation: at week 24 follow up
Secondary	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 3 through 26.	Retention: through week 26
Secondary	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.	Retention: at week 26
Secondary	Discontinuation KS1: Other discontinuation outcomes	Participants who did not meet the criteria for the primary outcome (Completed Discontinuation without Relapse), will be subcategorized into 3 other outcome categories: 1) Did not Complete Discontinuation (i.e., MOUD is continued or discontinued and then restarted within the next 24 weeks) and did not Relapse; 2) Completed Discontinuation followed by Relapse; or 3) Did not Complete Discontinuation and Relapse (i.e., relapse while on MOUD).	Discontinuation: at week 24 follow up
Secondary	DSK2: 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).	Discontinuation: week 24 follow up