A Strategy to Improve Success of Treatment Discontinuation in Buprenorphine Responders

This study is an open--label randomized outpatient trial to evaluate feasibility and efficacy of rapid buprenorphine (BUP) discontinuation followed by brief course of treatment with long--acting naltrexone (XR--NTX) and to compare it to the standard method of gradual BUP taper.Individuals with opioid use disorder (OUD) (N=60) who have successfully completed at least 6 months of buprenorphine treatment and do not wish to remain in a long--term buprenorphine maintenance program will be recruited. The first phase includes a 4--week period of stabilization on buprenorphine 4--8 mg at the research clinic to assure that patients are stable, compliant, and free from illicit opioids. Participants that meet the above criteria will be randomized 1:1 to: 1) buprenorphine discontinuation and outpatient transition to XR--NTX with 3 monthly injections, or 2) buprenorphine discontinuation using a gradual 5-week long taper. In both groups participants will receive weekly relapse prevention therapy and will be monitored for the duration of the trial, which is 25 weeks post randomization.

Study Overview

• Status: Completed
• Conditions: Opioid-use Disorder
• Intervention / Treatment: Drug: Vivitrol; Drug: Buprenorphine

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A documented history of treatment with buprenorphine or buprenorphine/naloxone for at least 6 months with sustained abstinence from illicit opioids for at least 3 months. Participants must be maintained on daily dose of buprenorphine in the 4--8 mg range.(MINI interview by therapist, Clinical interview by psychiatrist, consultation with previous prescriber or the verification patients's self-report with the prescribing records (PMP) with patient's permission).
2. Aged 18 to 60 years (Clinical interview).
3. In otherwise good health based on complete medical history, physical examination, vital signs measurement, ECG, and laboratory tests (hematology, blood chemistry, urinalysis) within normal ranges (Medical history and physical examination by psychiatrist or NP, laboratory tests (serum Chem-20 and CBC, urinalysis), ECG).
4. Seeking buprenorphine discontinuation and willing to accept randomization to either taper from buprenorphine or injection naltrexone (clinical interview).

Exclusion Criteria:

1. Lifetime history of DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder (MINI interview by therapist, Clinical interview by psychiatrist).
2. Current DSM-5 criteria for any other psychiatric disorder that in the investigator's judgment is unstable, would be disrupted by the study medication, or is likely to require pharmacotherapy or psychotherapy during the study period. Concurrent treatment with other psychotropic medication is exclusionary. ( MINI interview by therapist, Clinical interview and mental status exam by psychiatrist, contact with collateral information as needed and available).
3. Individuals who meet DSM-5 criteria for any substance use disorders - severe, other than opioid and nicotine use disorder. Physiological dependence on alcohol or sedative-hypnotics is exclusionary. (MINI interview by therapist, Clinical interview by psychiatrist).
4. A recent history of binge-use of alcohol or sedative-hypnotics (using large amounts in a short time to severe intoxication or blackouts). (Clinical interview by psychiatrist).
5. Pregnancy, lactation, or failure to use adequate contraceptive method in female patients who are currently engaging in sexual activity with men. ( Clinical interview by psychiatrist, physical examination and medical history by psychiatrist or NP, urine pregnancy test, serum HCG).
6. Unstable medical conditions, such as AIDS, cancer, uncontrolled hypertension (blood pressure > 140/90), uncontrolled diabetes, pulmonary hypertension or heart disease. (Medical history and physical examination by psychiatrist or NP, laboratory tests (serum Chem-20 and CBC, urinalysis), ECG).
7. Legally mandated to participate in a substance use disorder treatment program ( Participant self-report, Clinical interview by psychiatrist).
8. Current or recent history of significant violent or suicidal behavior, risk for suicide or homicide (MINI interview by therapist, Clinical interview by psychiatrist).
9. History of accidental opioid overdose in the last three years or any other significant history of overdose following detoxification within past 10 years defined as an episode of opioid-induced unconsciousness, whether or not medical treatment was sought or received. ( MINI interview by therapist, Clinical interview by psychiatrist).
10. Elevated liver function tests (AST and ALT > 3 times the upper limit of normal) ( Laboratory tests -serum Chem-20).
11. Known history of allergy, intolerance, or hypersensitivity to naltrexone or any other study medications( Participant self-report, Clinical interview by psychiatrist).

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: Regimen 1; Rapid Monday to Friday oral naltrexone-induction procedure	Drug: Vivitrol; Oral naltrexone induction procedure followed by Vivitrol
Experimental: Regimen 2; 5-week buprenorphine taper from maintenance dose of 8, 6, or 4mg	Drug: Buprenorphine; 5-week buprenorphine taper

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Patients Successfully Transitioned Off Buprenorphine	Percent of patients retained in treatment and abstinent from opioids at the end of the trial	Week 25

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: July 25, 2017
• First Submitted That Met QC Criteria: July 25, 2017
• First Posted (Actual): July 28, 2017

Study Record Updates

• Last Update Posted (Actual): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: buprenorphine; opioid dependence; Vivitrol; naltrexone
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: 7522 (Other Identifier: CTEP); 1R21DA042243 (U.S. NIH Grant/Contract)

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