Buprenorphine/Naloxone Stabilization and Induction Onto Injection Naltrexone
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|ClinicalTrials.gov Identifier: NCT02294253|
Recruitment Status : Completed
First Posted : November 19, 2014
Last Update Posted : October 31, 2018
|First Submitted Date ICMJE||November 17, 2014|
|First Posted Date ICMJE||November 19, 2014|
|Last Update Posted Date||October 31, 2018|
|Actual Study Start Date ICMJE||September 2014|
|Actual Primary Completion Date||December 2017 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Successful Induction onto XR-NTX [ Time Frame: One week after completing 30-day buprenorphone/naloxone stabilization/taper. ]
Proportion of participants inducted onto XR-NTX at the end of the 30-day buprenorphine/naloxone stabilization/taper.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT02294253 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Opioid Abstinence [ Time Frame: Collected 2x/week for 12 weeks post XR-NTX induction ]
Abstinence will be assessed by urine toxicology results collected 2x/week during the 12 week trial or for the length of participation
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Buprenorphine/Naloxone Stabilization and Induction Onto Injection Naltrexone|
|Official Title ICMJE||Buprenorphine/Naloxone Stabilization and Induction Onto Injection Naltrexone: An Outpatient Detoxification for Opioid Dependence.|
|Brief Summary||The investigators will randomize 50 opioid-dependent participants who have initially failed outpatient induction onto XR-NTX; participants will receive buprenorphine/naloxone on a weekly basis for 30 days. Buprenorphine/naloxone will be dispensed weekly during the 30-day stabilization and twice weekly during taper phase, and all patients who successfully complete the detoxification will be offered induction onto XR-NTX. All participants will receive weekly therapy with a study psychiatrist. All participants will receive open-label medication. The primary outcome of this study will be percentage of patients successfully inducted onto XR-NTX. Secondary outcomes will be time to relapse, defined as opioid use or dropout.|
Buprenorphine induction/stabilization/taper: Buprenorphine induction will be conducted at our STARS clinic and according to current clinical guidelines. Participants who have initially failed outpatient induction onto XR-NTX will receive buprenorphine/naloxone (BUP) on a weekly basis that they will take daily, according to the following schedule: 8/2 mg (Days 1-10), 6/1.5 mg (Days 11-15), 4/1 mg (Days 16-20), 3.0/0.75 mg (Days 21-25), 2.0/0.5 mg (Days 26-30).
Participants will attend the clinic twice weekly and will be assessed for opioid and other substance use (urine toxicology and self-report), vital signs, opioid withdrawal symptoms, opioid cravings, and dose adjustments of buprenorphine will be made as needed by study physicians. If a dose reduction is needed, the stabilization and taper schedule will be adjusted to occur over 30 days.
Participants will be stabilized on, and tapered off, buprenorphine over a 4-week period.Reductions will occur in a graded fashion, with the stabilization dose reduced to 2 mg. This approach to buprenorphine taper is intended to resemble standard clinical practice, in which patients seeking transition off buprenorphine undergo a slow taper. A gradual taper over approximately 4 weeks has established precedent (Sigmon et al. 2013, Ling et al. 2009, Nielsen et al. 2013) as a well-tolerated taper strategy for transitioning off buprenorphine. The purpose is in part to provide a slow transition with minimal withdrawal symptoms. Participants will have at least two study visits a week during the buprenorphine taper, but may be seen more regularly at STARS if deemed clinically necessary.
Naltrexone induction procedure: Participants who successfully complete the taper must then complete a two-day washout (abstinence for opioids, buprenorphine). During this 48-hr period,participants will report to the STARS clinic daily for vital sign monitoring and to receive ancillary medications (clonidine, clonazepam, zolpidem, prochlorperazine) to alleviate withdrawal and discomfort as needed. After abstinence of >/=48 hours from the last buprenorphine dose, to allow for mu receptor availability, participants will begin the naltrexone induction,using a 4-day ascending taper of oral naltrexone (1, 3, 12, and 25 mg), followed by injection naltrexone . The administration of naltrexone will occur within a detoxification suite provided at STARS, consisting of a private room outfitted with two comfortable reclining lounge chairs for resting, adjustable lighting, and an entertainment system. Participants will be monitored by clinical staff at least every 1-2 hours with frequent vital signs checks and withdrawal assessments. A research psychiatrist or study physician will be present at all times to conduct frequent clinical assessments and provide adjuvant medications and naltrexone. Patients will be monitored on a daily basis (Monday to Friday) for up to 8 hours per day. Transportation home by car service will be provided at the end of the day for any patient deemed to have this clinical need.
On Day 1 of the naltrexone induction,participants are pre-treated with prochlorperazine 10 mg for nausea, followed be the first dose of naltrexone 1mg. Ascending doses of naltrexone will then be titrated upward slowly (3mg, 12mg, 25mg). Adjuvant medications will be available to patients and will include clonidine for myalgias, prochlorperazine for nausea, clonazepam to reduce anxiety and dysphoria, and trazodone or zolpidem for insomnia. Participants will be provided take-home doses of adjuvant medications in small doses and on a tapering schedule for one week post-administration of XR-NTX. Participants will be required to visit the clinic daily and remain there for at least 1 hour to permit close monitoring, with an option to stay as long as necessary to achieve relief of symptoms and medical stability prior to being discharged home.
Once 25 mg of naltrexone has been tolerated, the participant may receive 380 mg IM XR-NTX.
Additionally, for female participants, a urine pregnancy test will be obtained on the day of XR-NTX administration. Prior to administration of XR-NTX, participants who have been non-compliant with the oral naltrexone schedule, accompanied by lapses to opioid use, or in any case for which the challenge appears clinically indicated in the judgment of the study physician or research team, will receive a naloxone challenge prior to XR-NTX administration. Referrals to local treatment providers will be arranged for participants who successfully complete the study and request to continue XR-NTX maintenance
XR-NTX injections: XR-NTX will be administered once naltrexone 25 mg has been tolerated, as an intramuscular injection (380 mg) in one buttock by one of the research psychiatrists or research nurses of STARS, who are currently trained and administer XR-NTX in other protocols. Participants will be observed for at least 2 hours after the first injection. Participants will be offered a second injection at Week 5 (four weeks post-administration of the first injection), and a third injection at Week 9. Prior to receiving second and third injections at STARS, patients will either provide an opioid-negative urine or pass a naloxone challenge test.
At each STARS visit the patient meets with the research assistant to complete research ratings, including self-report of withdrawal, mood, and drug use. Blood samples are drawn according to the protocol for naltrexone serum levels and liver enzymes. The patient provides a urine sample under observation by a staff member at each visit. STARS is staffed by both male and female research assistants so that all urines can be appropriately monitored.
All participants will receive a weekly medication adherence-focused psychosocial intervention informed by relapse prevention strategies we previously developed in Behavioral Naltrexone Therapy and delivered by the study physician (Rothenberg, Sullivan et al. 2002). We have developed a relapse prevention approach which includes an emphasis on compliance with NTX. Participants will receive this therapy during weekly visits in outpatient Weeks 1-12 following induction onto XR-NTX.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Opioid Dependence|
|Intervention ICMJE||Drug: Buprenorphine/naloxone
30 day oral Buprenorphine/naloxone
Other Name: Suboxone
|Study Arms ICMJE||Experimental: Buprenorphine/naloxone stabilization
Participants who have initially failed outpatient induction onto XR-NTX will receive buprenorphine/naloxone (BUP) on a weekly basis that they will take daily,
Intervention: Drug: Buprenorphine/naloxone
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||December 2017|
|Actual Primary Completion Date||December 2017 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
3.) Pregnancy, lactation, or failure in a sexually active woman to use adequate contraceptive methods. 4) Active medical illness which might make participation hazardous, such as untreated hypertension, acute hepatitis with AST or ALT > 3 times normal, AIDS, unstable diabetes.
5) Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-5 Schizophrenia or any psychotic disorder, severe Major Depressive Disorder, or suicide risk or 1 or more suicide attempts within the past year.
6) Physiologically dependent on alcohol or sedative-hypnotics with impending withdrawal. Other substance use diagnoses are not exclusionary.
7) History of allergic or adverse reaction to buprenorphine, naltrexone, naloxone, clonidine, or clonazepam.
8) Chronic organic mental disorder (e.g. AIDS dementia). 9) History of accidental drug overdose in the last 3 years as defined as an episode of opioid-induced unconsciousness or incapacitation, whether or not medical treatment was sought or received.
10) Painful medical condition that requires ongoing opioid analgesia or anticipated surgery necessitating opioid medications.
|Ages ICMJE||18 Years to 60 Years (Adult)|
|Accepts Healthy Volunteers ICMJE||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT02294253|
|Other Study ID Numbers ICMJE||6999|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Elizabeth Evans, New York State Psychiatric Institute|
|Study Sponsor ICMJE||New York State Psychiatric Institute|
|Collaborators ICMJE||National Institute on Drug Abuse (NIDA)|
|PRS Account||New York State Psychiatric Institute|
|Verification Date||October 2018|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP