Opioid Use Disorder (OUD)
Conditions
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.
Interventions
DRUGSL-BUP
Daily dosing of sublingual buprenorphine-naloxone
DRUGXR-BUP
Weekly/monthly dosing of extended-release injectable buprenorphine
DRUGXR-NTX
Monthly dosing of extended-release injectable naltrexone
BEHAVIORALMM
MM consists of standard Medical Management and the usual counseling at the treatment program.
BEHAVIORALMMR
MMR consists of Medical Management and usual counseling, plus a technology-based behavioral component.
BEHAVIORALMMD
MMD consists of Medical Management and usual counseling, plus a technology-based behavioral component.
Sponsors
NYU Langone Health
New York State Psychiatric Institute
Columbia University
Harvard Medical School (HMS and HSDM)
Mclean Hospital
National Institute on Drug Abuse (NIDA)
The Emmes Company, LLC
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention: Continuous retention in MOUD treatment through 26 weeks | Retention: from randomization through week 26 | 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. |
| Discontinuation: Completed Discontinuation without Relapse | Discontinuation: from randomization through week 24 follow up | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retention KS1: Weekly opioid abstinence | Retention: from randomization through week 26 | Weekly opioid abstinence (measured by Timeline Followback, not contradicted by toxicology test). Repeated yes/no measure for each of weeks 1 through 26. |
| Retention KS2: Treatment effectiveness | Retention: at week 26 | 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 KS3: Treatment by baseline severity | Retention: at week 26 | Treatment by baseline severity interaction where severity is indicated by the randomization stratum injection use (yes/no). |
| Discontinuation KS1: Completed Discontinuation | Discontinuation: from randomization through week 24 follow up | Completed Discontinuation without regard to relapse status |
| Discontinuation KS2: Relapse | Discontinuation: from randomization through week 24 follow up | Relapse - separate binary outcome without regard to discontinuation status |
| Discontinuation KS3: Safety | Discontinuation: from randomization through week 24 follow up | Safety outcomes (binary, any one or more occurrences): overdoses, all non-fatal plus fatal. |
| Discontinuation KS4: Treatment effectiveness | Discontinuation: at end of taper (EoT) and week 24 follow up | 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREdward V Nunes, MD
New York State Psychiatric Institute/Columbia University Irving Medical Center
PRINCIPAL_INVESTIGATORJohn Rotrosen, MD
NYU Langone Health
PRINCIPAL_INVESTIGATORRoger Weiss, MD
Harvard Medical School/McLean Hospital
Outcome results
None listed