Stable Opioid DependencePhase 1/2NCT01895036
Nalrexone Facilitated Discontinuation of Buprenorphine
A Phase 1/2 study testing Naltrexone in people with Stable Opioid Dependence, run by New York State Psychiatric Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 49 years
- Conditions the study is for
- Stable Opioid Dependence
- What is being tested?
- Naltrexone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Sep 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Naltrexone
- Keywords
- maintained on 2 mg or less of buprenorphine, in which discontinuation of agonist treatment is clinically feasible but difficult
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
Also called Vivitrol
| Study group | Role | What they receive |
|---|---|---|
| Naltrexone | Experimental | PO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone Receives: Drug: Naltrexone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Successful Discontinuation of Buprenorphine
Number of individuals successfully discontinuing buprenorphine during the inpatient phase and through follow-up.
Measured: 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2013 (estimated)
- Study startFeb 2011
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stable Opioid DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Elias Dakwar, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01895036
- Sponsor's protocol ID
- 6332
- Status last verified
- Jun 2018
- First submitted
- 3 Jul 2013
- Last updated
- 15 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nalrexone Facilitated Discontinuation of Buprenorphine
- ClinicalTrials.gov ID
- NCT01895036
- Acronym / sponsor ID
- 6332
- Conditions
- Stable Opioid Dependence
- Keywords
- maintained on 2 mg or less of buprenorphine, in which discontinuation of agonist treatment is clinically feasible but difficult
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Feb 2011
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 10 Jul 2013 (estimated)
- Results
- Posted 6 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Naltrexone | Experimental | Drug: NaltrexonePO naltrexone titration on a mixed inpatient/outpatient basis, followed by administration of Vivitrol four days following the 1st dose of naltrexone |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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,
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaltrexoneAlso: Vivitrol | Drug | Naltrexone |
Primary outcome
Successful Discontinuation of Buprenorphine
Time frame: 7 weeks
Number of individuals successfully discontinuing buprenorphine during the inpatient phase and through follow-up.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Naltrexone in people with Stable Opioid Dependence, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Successful Discontinuation of Buprenorphine (time frame: 7 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2018.