Clinical trial NCT04464980: Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (RDD)
Official title: NIDA-CTN-0100: Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (RDD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Opioid Use Disorder (OUD)
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: New York State Psychiatric Institute
name: Columbia University
name: Harvard Medical School (HMS and HSDM)
name: Mclean Hospital
name: National Institute on Drug Abuse (NIDA)
name: The Emmes Company, LLC
First posted: 2020-07-09
Enrollment: 2190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention 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
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Retention: Continuous retention in MOUD treatment at 26 weeks
timeFrame: Retention: at week 26
measure: Discontinuation: Completed Discontinuation without Relapse
timeFrame: Discontinuation: at week 24 follow up
Secondary outcomes:
measure: Retention KS1: Weekly opioid abstinence
timeFrame: Retention: through week 26
measure: Retention KS2: Treatment effectiveness
timeFrame: Retention: at week 26
measure: Discontinuation KS1: Other discontinuation outcomes
timeFrame: Discontinuation: at week 24 follow up
measure: DSK2: Treatment effectiveness
timeFrame: Discontinuation: week 24 follow up
Other outcomes:
measure: R-Other 1a: Continuous opioid abstinence-weeks 23-26
timeFrame: Retention: weeks 23-26
measure: R-Other 1b: Continuous opioid abstinence-weeks 47-50
timeFrame: Retention: weeks 47-50
measure: R-Other 1c: Continuous opioid abstinence-weeks 71-74
timeFrame: Retention: weeks 71-74
measure: R-Other 2: Weekly opioid abstinence
timeFrame: Retention: weeks 27-74
measure: R-Other 3: Weekly abstinence from other substance use
timeFrame: Retention: weeks 0-74
measure: R-Other 4: Craving
timeFrame: Retention: weeks 0-98
measure: R-Other 5a: Stable abstinence at week 26
timeFrame: Retention: week 26
measure: R-Other 5b: Stable abstinence at week 50
timeFrame: Retention: week 50
measure: R-Other 5c: Stable abstinence at week 74
timeFrame: Retention: week 74
measure: R-Other 6: Retention in MOUD at week 50
timeFrame: Retention: week 50
measure: R-Other 7: Retention in MOUD at week 74
timeFrame: Retention: week 74
measure: R-Other 8: Dropout from MOUD treatment
timeFrame: Retention: weeks 0-74
measure: R-Other 9: Depression
timeFrame: Retention: weeks 0-26
measure: R-Other 10: Anxiety
timeFrame: Retention: weeks 0-26
measure: R-Other 11: Stress
timeFrame: Retention: weeks 0-26
measure: R-Other 12: Pain
timeFrame: Retention: weeks 0-26
measure: R-Other 13: Recovery capital
timeFrame: Retention: weeks 0-26
measure: R-Other 14: Negative consequences of opioid use
timeFrame: Retention: weeks 0-26
measure: R-Other 15: Sexual risk
timeFrame: Retention: weeks 0-26
measure: R-Other 16: Rate of incarceration
timeFrame: Retention: weeks 0-26
measure: R-Other 17: Rate of homelessness
timeFrame: Retention: weeks 0-26
measure: D-Other 1: Relapse
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 2: Withdrawal symptoms
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 3: Craving
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 4: Depression
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 5: Anxiety
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 6: Stress
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 7: Pain
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 8a: Recovery capital (BARC-10)
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 8b: Recovery capital (RCS)
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 9: Negative consequences of opioid use
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 10: Sexual risk
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 11: Rate of incarceration
timeFrame: Discontinuation: during taper and through week 24 follow up
measure: D-Other 12: Rate of homelessness
timeFrame: Discontinuation: during taper and through week 24 follow up
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences (UAMS) / Center for Addiction Services and Treatment (CAST)
state: Arkansas
city: Tarzana
country: United States
facility: Tarzana Treatment Centers, Inc.
state: California
city: Bridgeport
country: United States
facility: Liberation Programs, Inc.
state: Connecticut
city: Clearwater
country: United States
facility: Operation PAR
state: Florida
city: Jacksonville
country: United States
facility: Gateway Community Services
state: Florida
city: Orlando
country: United States
facility: Aspire Health Partners
state: Florida
city: Baltimore
country: United States
facility: Mountain Manor / Maryland Treatment Centers
state: Maryland
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
city: Fall River
country: United States
facility: Stanley Street Treatment and Resources, Inc.
state: Massachusetts
city: Newton
country: United States
facility: Square Medical Group, LLC
state: Massachusetts
city: Cape Girardeau
country: United States
facility: Gibson Center for Behavioral Change
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock - ATP
state: New Hampshire
city: Albuquerque
country: United States
facility: University of New Mexico Addiction and Substance Abuse Program
state: New Mexico
city: New York
country: United States
facility: Bellevue Hospital Center
state: New York
city: Roseburg
country: United States
facility: Adapt Integrated Health Care
state: Oregon
city: Winston
country: United States
facility: Adapt Integrated Health Care
state: Oregon
city: Pittsburgh
country: United States
facility: Center for Psychiatric and Chemical Dependency Services (CPCDS)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Internal Medicine Recovery Engagement Program (IM-REP)
state: Pennsylvania
city: Conway
country: United States
facility: Shoreline Behavioral Health Services
state: South Carolina
city: Salt Lake City
country: United States
facility: Huntsman Mental Health Institute / University of Utah
state: Utah
city: Morgantown
country: United States
facility: Chestnut Ridge Center
state: West Virginia
Study officials:
affiliation: New York State Psychiatric Institute/Columbia University Irving Medical Center
name: Edward V Nunes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NYU Langone Health
name: John Rotrosen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard Medical School/McLean Hospital
name: Roger Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References: