Completed

NCT Number: NCT01895036

Nalrexone Facilitated Discontinuation of Buprenorphine

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.

Completed

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Key information

Conditions

Stable Opioid Dependence

Age range

18 year–49 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

NYSPI

New York, 10032, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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.

Treatment and study plan

Naltrexone

Drug

Other names: Vivitrol

Primary outcomes

Successful Discontinuation of Buprenorphine

Time frame: 7 weeks

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

Sponsors and collaborators

Lead sponsor

New York State Psychiatric Institute

Other

Collaborators

National Institute on Drug Abuse (NIDA)

Registry information

Important dates

Study start: 2011
Primary completion: 2013
Study completion: 2013
First posted: Jul 10, 2013
Registry last updated: Jun 15, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.