Nalrexone Facilitated Discontinuation of Buprenorphine

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01895036
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 31
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The efficacy of buprenorphine as a long-term agonist treatment has been offset by the emergence of intolerable withdrawal phenomena in a subset of individuals on chronic maintenance who attempt to discontinue the medication. Efforts are needed to better understand these challenges encountered with buprenorphine, as well as to develop interventions to facilitate medication discontinuation.

Emerging evidence suggests that these difficulties may be related to the unique effects of buprenorphine on sites other than mu-opioid receptors, such as kappa-opioid receptors. Kappa-opioid agonism produces aversive, dysphoric-like effects, and can also increase the likelihood of reinstatement to drug use through stress-mediated mechanisms. Some of the discomfort observed during drug taper may therefore be due to the attenuation or loss of kappa-opioid antagonism afforded by buprenorphine, as well as to rebound kappa-opioid activation. Naltrexone represents a promising candidate for extending kappa blockade and therefore for facilitating discontinuation attempts. Naltrexone and its active metabolite 6-Beta-naltrexol are competitive antagonists at the mu and kappa receptors, and to a lesser extent at the delta receptor. Naltrexone and buprenorphine have comparable affinity for the mu-opioid receptor and thus buprenorphine is displaced by naltrexone more gradually than are other opioids with less affinity; a careful titration of naltrexone is less likely, therefore, to precipitate severe withdrawal states in individuals coming off buprenorphine, and the two have been combined to good effect in other settings.

The purpose of this study is therefore to investigate the feasibility of naltrexone augmentation on discontinuing buprenorphine in eligible patients on long-term maintenance.

Condition or Disease	Intervention/Treatment	Phase
Stable Opioid Dependence	Drug: Naltrexone	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naltrexone PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone	Drug: Naltrexone; Other Names: Vivitrol

Outcome Measures

Primary Outcome Measures

1. Successful Discontinuation of Buprenorphine [7 weeks]

   Number of individuals successfully discontinuing buprenorphine during the inpatient phase and through follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult, aged 18-49.

2. Currently maintained on buprenorphine, with a clinically acceptable interest in tapering or discontinuing it

3. Willingness to switch over to naltrexone

4. 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.

5. Able to give informed consent and comply with study procedures,

6. Currently on 2 mg or less of buprenorphine.

7. Voluntarily seeking treatment for opioid dependence.

Exclusion Criteria:

1. Significant current suicidal risk or 1 or more suicide attempts within the past year

2. History of accidental drug overdose in the last three years defined as an episode of opioid-induced unconsciousness or incapacitation, whether or not medical treatment was sought or received.

3. Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory method of birth control

4. Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-IV organic mental disorder, psychotic disorder, or bipolar disorder with mania

5. History of allergic reaction, adverse reaction, or sensitivity to any study medication.

6. Acute hepatitis with SGOT or SGPT > 3 times the upper end of the laboratory normal range (chronic hepatitis is acceptable as we have found naltrexone treatment well tolerate and safe among patients with chronic hepatitis)

7. Currently prescribed or regularly taking opioids for chronic pain

8. Current participation in another intensive psychotherapy or substance abuse treatment program, or participation in another treatment study.

9. Opioid dependence is not well-managed, and characterized by relapses, slips, or missed doses

10. Concurrent treatment with psychotropic medications which may interact adversely with naltrexone, such as duloxetine and valproic acid.

Contacts and Locations

Locations

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

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elias Dakwar, research psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01895036
• Other Study ID Numbers: 6332
• First Posted: Jul 10, 2013
• Last Update Posted: Jun 15, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Elias Dakwar, research psychiatrist, New York State Psychiatric Institute: maintained on 2 mg or less of buprenorphine, in which discontinuation of agonist treatment is clinically feasible but difficult
• Additional relevant MeSH terms: Opioid-Related Disorders; Naltrexone

Study Results

Participant Flow

Arm/Group Title	Naltrexone
Arm/Group Description	PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone Naltrexone
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Naltrexone
Arm/Group Description	PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone Naltrexone
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.2 (16.3)
Sex: Female, Male (Count of Participants)
Female	2 33.3%
Male	4 66.7%
Region of Enrollment (Count of Participants)
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Successful Discontinuation of Buprenorphine
Description	Number of individuals successfully discontinuing buprenorphine during the inpatient phase and through follow-up.
Time Frame	7 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naltrexone
Arm/Group Description	PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone Naltrexone
Measure Participants	6
Count of Participants [Participants]	6 100%

Adverse Events

Time Frame	Beginning with entry into the protocol and through 1 month after study completion.
Arm/Group Title	Naltrexone
Arm/Group Description	PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone Naltrexone
All Cause Mortality
	Naltrexone
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Naltrexone
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Naltrexone
	Affected / at Risk (%)	# Events
Total	0/6 (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.