Nalrexone Facilitated Discontinuation of Buprenorphine
Primary Purpose
Stable Opioid Dependence
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Naltrexone
Sponsored by
About this trial
This is an interventional treatment trial for Stable Opioid Dependence focused on measuring maintained on 2 mg or less of buprenorphine, in which discontinuation of agonist treatment is clinically feasible but difficult
Eligibility Criteria
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.
Sites / Locations
- NYSPI
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Naltrexone
Arm Description
PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone
Outcomes
Primary Outcome Measures
Successful Discontinuation of Buprenorphine
Number of individuals successfully discontinuing buprenorphine during the inpatient phase and through follow-up.
Secondary Outcome Measures
Full Information
NCT ID
NCT01895036
First Posted
July 3, 2013
Last Updated
June 13, 2018
Sponsor
New York State Psychiatric Institute
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT01895036
Brief Title
Nalrexone Facilitated Discontinuation of Buprenorphine
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York State Psychiatric Institute
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stable Opioid Dependence
Keywords
maintained on 2 mg or less of buprenorphine, in which discontinuation of agonist treatment is clinically feasible but difficult
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Naltrexone
Arm Type
Experimental
Arm Description
PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone
Intervention Type
Drug
Intervention Name(s)
Naltrexone
Other Intervention Name(s)
Vivitrol
Primary Outcome Measure Information:
Title
Successful Discontinuation of Buprenorphine
Description
Number of individuals successfully discontinuing buprenorphine during the inpatient phase and through follow-up.
Time Frame
7 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
NYSPI
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
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Nalrexone Facilitated Discontinuation of Buprenorphine
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