A Clinical Trial Comparing Buprenorphine Formulations for High Potency Synthetic Opioid Use

A Randomized Controlled Trial Examining Extended-Release Injectable Buprenorphine in Those Who Use High Potency Synthetic Opioids

The goal of this clinical trial is to compare buprenorphine formulations (sublingual buprenorphine versus long-acting injectable buprenorphine) for treating opioid use disorder among individuals who use fentanyl and/or other high potency synthetic opioids. Individuals aged 18-65 will be eligible for enrollment. The main questions it aims to answer are:

Are there differences in frequency of drug use after individuals start treatment with sublingual buprenorphine compared to injectable buprenorphine?

Are there differences in rates of sustained relapse after individuals start treatment with sublingual buprenorphine compared to injectable buprenorphine?

Investigators also seek to understand and explore:

How factors like body fat, body weight, and quantity of fentanyl use before treatment influence treatment outcomes.

How blood levels of buprenorphine and its metabolite norbuprenorphine early on in treatment may influence treatment outcomes.

How factors like craving and opioid withdrawal symptoms influence treatment outcomes.

Participants will:

Complete a brief overnight hospital stay in an inpatient research unit. This hospital stay will enable participants to start treatment with either sublingual buprenorphine or injectable buprenorphine.

Provide blood and urine samples while on the inpatient unit and at follow up.

Complete in-person follow up visits at 1-, 2-, 3- and 4-weeks after leaving the hospital to measure drug use, craving, withdrawal, quality of life, and physical health.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Buprenorphine Injection; Drug: Buprenorphine + naloxone (Suboxone)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Rachel Luba, PhD; Phone Number: 646-774-8189; Email: RRL2117@CUMC.Columbia.edu
• Study Contact Backup: Name: John Mariani, MD; Phone Number: 212-923-3031; Email: jm2330@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10019
      • Recruiting
      • Substance Treatment and Research Service
      • Contact: Administrative assistant; Phone Number: 646-774-8189; Email: RRL2117@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 to 65
• Voluntarily seeking treatment for opioid use disorder (OUD)
• Consistent use of fentanyl or other high potency synthetic opioids
• Meets DSM-5 criteria for OUD with at least moderate severity
• Able to provide written informed consent in English and willing to comply with study procedures

Exclusion Criteria:

• Meets DSM-5 criteria for another substance use disorder as the primary diagnosis
• Has an active, unmanaged psychiatric condition that would make participation hazardous (e.g., acute, psychosis, current suicidality, current manic episode)
• Has an active, unmanaged medical condition that would make participation hazardous or preclude use of buprenorphine or ancillary medications for withdrawal (e.g., unmanaged hypertension, unmanaged diabetes, clinically significant abnormality on ECG, acute hepatitis)
• Buprenorphine or methadone treatment in the past 30 days
• Known allergy, hypersensitivity or intolerance to buprenorphine
• Pregnancy, lactation, or unwillingness to use adequate contraceptive methods
• Current physiological dependence on sedative-hypnotics or alcohol that would require medically supervised detoxification
• Liver function tests > 2x the upper limit of normal
• Use of medications or herbal products with known CYP3A4 inhibition or induction properties in the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Injectable Buprenorphine; Long-Acting Injectable Buprenorphine administered after participants receive and tolerate a single 4/1 mg sublingual buprenorphine/naloxone dose	Drug: Buprenorphine Injection; Participants randomized to injectable buprenorphine naloxone will receive a 300mg injection after receiving/tolerating a single 4/1 mg sublingual buprenorphine/naloxone dose
Active Comparator: Sublingual Buprenorphine/Naloxone; Titration onto sublingual buprenorphine/naloxone (standard of care)	Drug: Buprenorphine + naloxone (Suboxone); Participants randomized to sublingual buprenorphine naloxone will initiate treatment based on clinical guidelines/standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Days Abstinent from Opioids	Abstinence from Opioids (% days abstinent; continuous; longitudinal) during each week of the 4 week follow up period measured via the timeline follow back.	4 week follow up period
Sustained Relapse	Sustained relapse during the 4 week follow up period (binary), defined as 5 consecutive days of illicit opioid use reported on the timeline follow back at any point during the 4 week follow up period.	4 week follow up period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Peak Clinical Opiate Withdrawal Scale (COWS) score	The time to peak Clinical Opiate Withdrawal Scale (COWS) score during the induction period (time-to-event/survival). The COWS ranges from 0-48 with higher scores indicating more severe opioid withdrawal symptoms.	During the inpatient induction period (approximately 1 overnight stay)
Peak Clinical Opiate Withdrawal Scale (COWS) score	The peak Clinical Opiate Withdrawal Scale (COWS) score during the induction period (continuous). The COWS ranges from 0-48 with higher scores indicating more severe opioid withdrawal symptoms.	During the inpatient induction period (approximately 1 overnight stay)
Dropout during induction	Dropout during the induction period (binary)	During the inpatient induction period (approximately 1 overnight stay)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome 1: Craving	Craving as reported on the Opioid Craving Visual Analog Scale OC-VAS (longitudinal; continuous) during induction and follow up. The OC-VAS ranges from 0-100mm with higher ratings indicating more intense/severe craving.	Induction Period (Overnight Inpatient Stay) and 4-week follow up period
Exploratory Outcome 2: Clinical Opiate Withdrawal Scale (COWS) Score	Opioid Withdrawal Symptoms as reported on the Clinical Opiate Withdrawal Scale (COWS; longitudinal; continuous) during induction and follow up. The COWS ranges from 0-48 with higher scores indicating more severe opioid withdrawal symptoms.	Induction Period (Overnight Inpatient Stay) and 4-week follow up period
Exploratory Outcome 3: Time to first use of illicit opioids	Time to first use of illicit opioids during the 4-week follow up period (time-to-event/survival)	4-week follow up period

Collaborators and Investigators

• Sponsor: Rachel R. Luba
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2026
• Primary Completion (Estimated): January 15, 2029
• Study Completion (Estimated): January 15, 2029

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 5, 2024
• First Posted (Actual): December 10, 2024

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Drug Combinations; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Buprenorphine, Naloxone Drug Combination; Buprenorphine; Naloxone
• Other Study ID Numbers: AAAV2503; K23DA057392-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to NIDA's policy for data management and sharing, de-identified data will be deposited into the NAHDAP repository.
• IPD Sharing Time Frame: De-identified data will be made available no later than when the primary outcome paper is published or when the award ends. The data will be stored in the repository for at least 10 years after the funding period ends.
• IPD Sharing Access Criteria: Once released to the repository, the investigator will not control data access.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No