A Strategy to Improve Success of Treatment Discontinuation in Buprenorphine Responders

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT03232346
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 2
• Actual Duration (Months): 46.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Opioid-use Disorder	Drug: Vivitrol; Drug: Buprenorphine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Strategy to Improve Success of Treatment Discontinuation in Buprenorphine Responders
• Actual Study Start Date: Aug 1, 2017
• Actual Primary Completion Date: Jun 30, 2021
• Actual Study Completion Date: Jun 30, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percent of Patients Successfully Transitioned Off Buprenorphine [Week 25]

   Percent of patients retained in treatment and abstinent from opioids at the end of the trial

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form - Apr 2, 2019
• Statistical Analysis Plan - Nov 15, 2017

More Information

Publications

None provided.

• Responsible Party: Adam Bisaga, Research Psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT03232346
• Other Study ID Numbers: 7522
• First Posted: Jul 28, 2017
• Last Update Posted: Jun 21, 2022
• Last Verified: May 1, 2022

• 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
• Keywords provided by Adam Bisaga, Research Psychiatrist, New York State Psychiatric Institute: buprenorphine; naltrexone; Vivitrol; opioid dependence
• Additional relevant MeSH terms: Opioid-Related Disorders; Buprenorphine

Study Results

Participant Flow

Arm/Group Title	Regimen 1	Regimen 2
Arm/Group Description	Rapid Monday to Friday oral naltrexone-induction procedure Vivitrol: Oral naltrexone induction procedure followed by Vivitrol	5-week buprenorphine taper from maintenance dose of 8, 6, or 4mg Buprenorphine: 5-week buprenorphine taper
Period Title: Overall Study
STARTED	6	5
COMPLETED	2	3
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Regimen 1	Regimen 2	Total
Arm/Group Description	Rapid Monday to Friday oral naltrexone-induction procedure Vivitrol: Oral naltrexone induction procedure followed by Vivitrol	5-week buprenorphine taper from maintenance dose of 8, 6, or 4mg Buprenorphine: 5-week buprenorphine taper	Total of all reporting groups
Overall Participants	6	5	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	5 100%	11 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	41.7	49.6	45.3
Sex: Female, Male (Count of Participants)
Female	1 16.7%	0 0%	1 9.1%
Male	5 83.3%	5 100%	10 90.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 33.3%	1 20%	3 27.3%
Not Hispanic or Latino	4 66.7%	4 80%	8 72.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 20%	1 9.1%
White	5 83.3%	4 80%	9 81.8%
More than one race	1 16.7%	0 0%	1 9.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%	5 100%	11 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants who were randomized to one of the two study regimens

Arm/Group Title	Regimen 1	Regimen 2
Arm/Group Description	Rapid Monday to Friday oral naltrexone-induction procedure Vivitrol: Oral naltrexone induction procedure followed by Vivitrol	5-week buprenorphine taper from maintenance dose of 8, 6, or 4mg Buprenorphine: 5-week buprenorphine taper
Measure Participants	6	5
Count of Participants [Participants]	2 33.3%	3 60%

Adverse Events

Time Frame	7 months
Arm/Group Title	Regimen 1		Regimen 2
Arm/Group Description	Rapid Monday to Friday oral naltrexone-induction procedure Vivitrol: Oral naltrexone induction procedure followed by Vivitrol		5-week buprenorphine taper from maintenance dose of 8, 6, or 4mg Buprenorphine: 5-week buprenorphine taper
All Cause Mortality
	Regimen 1		Regimen 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)
Serious Adverse Events
	Regimen 1		Regimen 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/5 (20%)
Respiratory, thoracic and mediastinal disorders
hospitalization for pneumonia	0/6 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Regimen 1		Regimen 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.