Nalrexone Facilitated Discontinuation of Buprenorphine

NCT01895036 | Completed Phase 1 Results

• 1 other identifier: 6332
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Stable Opioid Dependence

Keywords

maintained on 2 mg or less of buprenorphine, in which discontinuation of agonist treatment is clinically feasible but difficult

Outcome Measures

Primary Outcomes (1)

• Successful Discontinuation of Buprenorphine

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

  7 weeks

Study Arms (1)

Naltrexone

EXPERIMENTAL

PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone

Drug: Naltrexone

Interventions

Naltrexone DRUG

Also known as: Vivitrol

Naltrexone

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult, aged 18-49.
• Currently maintained on buprenorphine, with a clinically acceptable interest in tapering or discontinuing it
• Willingness to switch over to naltrexone
• 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.
• Able to give informed consent and comply with study procedures,
• Currently on 2 mg or less of buprenorphine.
• Voluntarily seeking treatment for opioid dependence.

You may not qualify if:

• Significant current suicidal risk or 1 or more suicide attempts within the past year
• 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.
• Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory method of birth control
• 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
• History of allergic reaction, adverse reaction, or sensitivity to any study medication.
• 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)
• Currently prescribed or regularly taking opioids for chronic pain
• Current participation in another intensive psychotherapy or substance abuse treatment program, or participation in another treatment study.
• Opioid dependence is not well-managed, and characterized by relapses, slips, or missed doses
• Concurrent treatment with psychotropic medications which may interact adversely with naltrexone, such as duloxetine and valproic acid.

Sponsors & Collaborators

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

Study Sites (1)

NYSPI

New York, New York, 10032, United States

Location

MeSH Terms

Interventions

Naltrexone; vivitrol

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Linda Sherman
• Organization: NYSPI

lsherma@nyspi.columbia.edu

6467747158

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: research psychiatrist

Study Record Dates

• First Submitted: July 3, 2013
• First Posted: July 10, 2013
• Study Start: February 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: June 15, 2018
• Results First Posted: September 6, 2017

Record last verified: 2018-06

Locations

US (1)