Improved Strategies for Outpatient Opioid Detoxification
Condition: Opioid Dependence
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      The investigators will randomize 210 opioid-dependent participants to one of two outpatient
      detoxification strategies: (1) a standard 7-day buprenorphine induction and gradual taper
      from 8 mg to 0 mg vs. (2) 7-day oral naltrexone induction; both groups will receive a single
      administration of a Vivitrol injection: at Day 8 for the naltrexone induction group and Day
      15 for the buprenorphine group. The naltrexone arm is a modification of our current inpatient
      naltrexone induction procedure, consisting of a single day of buprenorphine followed by a
      washout day and 4 days of ascending oral naltrexone doses, prior to administering a dose of
      injectable naltrexone on Day 8. All participants will receive an intensive behavioral therapy
      for five weeks and will be followed for the subsequent 8 weeks to assess the longer-term
      outcome of the initial treatment. The primary outcome will be percentage of patients in each
      group successfully inducted onto Vivitrol. Key secondary outcomes will be 2-week abstinence
      at Weeks 4-5 (3rd and 4th weeks after Vivitrol injection), rates of completion of the 8-day
      detoxification, and percentage of patients in each group who return for additional Vivitrol
      injections in post-study follow-up. The main goal of this Stage 1a pilot study is to develop
      an improved outpatient opioid detoxification strategy, with particular relevance to newly
      diagnosed heroin addicts and prescription opioid abusers not seeking long-term agonist
      maintenance.

      Specific Aim #1: To develop procedures for outpatient opioid detoxification which include
      naltrexone to facilitate detoxification.

      Specific Aim #2: To compare injectable naltrexone induction rates between the naltrexone and
      buprenorphine groups following short-term outpatient opioid detoxification approach for
      initiating treatment for opioid dependence.
    

Detailed description: 
      We are proposing a randomized, parallel-groups 5-week study of relapse prevention in
      detoxified opioid-dependent individuals. This trial represents an initial test of the
      feasibility and efficacy of an outpatient opioid detoxification strategy employing induction
      onto long-acting naltrexone (Vivitrol), in combination with the recently adapted version of
      Behavioral Naltrexone Therapy for Depot Naltrexone (Depot-BNT). Participants will be
      randomized into one of two outpatient detoxification strategies: (1) standard 7-day
      buprenorphine induction and taper from 8 mg to 0 mg (N=33), followed on Day 15 by a naloxone
      challenge and a dose of long-acting injectable naltrexone (Vivitrol) (consistent with the
      FDA-approved recommendation of 7 or more days between last opioid dose and Vivitrol
      induction) vs. (2) a modification of our current inpatient naltrexone induction procedure,
      consisting of a single day of buprenorphine followed by a washout day and 4 days of ascending
      oral naltrexone doses, followed by long-acting injectable naltrexone (Vivitrol) 380 mg on Day
      8 (N=67). We are seeking to obtain Vivitrol samples from Alkermes; if we are successful in
      obtaining such samples, we will offer all participants who complete the study a second
      injection 4 weeks after the first, and a third injection will be offered at Week 12. All
      participants will receive an intensive behavioral therapy for five weeks and will be followed
      for up to 24 weeks to assess the long-term outcome of the initial treatment. Study
      assessments will be collected at baseline and at each study visit (twice weekly in Weeks 2-5;
      weekly in Weeks 6-9 for participants who receive a second Vivitrol injection and participate
      in follow-up care). Repeated assessments will also be completed at one and four months
      following the end of treatment. The primary aim of this study is to test the hypothesis that
      an outpatient opioid detoxification strategy using naltrexone will increase the likelihood of
      successful induction onto long-acting injectable naltrexone, compared to a buprenorphine
      taper in opioid-dependent patients. The primary outcome measure will be percentage in each
      treatment group (oral naltrexone vs. buprenorphine taper) receiving the Vivitrol injection at
      Day 8 or 15. Key secondary outcomes will be: two-week opioid abstinence during Weeks 4-5,
      retention in the 8-day detoxification procedure (time to dropout) and severity of opiate
      withdrawal during the first 5 weeks of treatment. We anticipate that the outpatient opioid
      detoxification method developed in this project will be uniquely suited to the needs of the
      rapidly expanding population of prescription opioid-abusing individuals seeking an
      alternative to opioid agonist maintenance. The current proposal will also yield important
      data on how to improve long-term outcomes for the buprenorphine taper method of opioid
      detoxification, through the addition of long-acting naltrexone.
    

Intervention name(s): oral naltrexone; Buprenorphine; Vivitrol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Following detoxification with buprenorphine (one dy of 8 mg) followed by oral naltrexone (ascending taper to 25 mg), participants will receive Vivitrol injection on Day 8. Behavioral therapy sessions will be offered for five weeks.; Following detoxification with buprenorphine [8-mg buprenorphine (Day 1) tapering to 0 mg (Day 7)] participants will receive Vivitrol injection on Day 15. Behavioral therapy sessions will be offered for five weeks.; dose of long-acting injectable naltrexone (Vivitrol 380 mg i.m. Injection)
Other intervention name(s): buprenorphine and oral naltrexone followed by Vivitrol; long-acting injectable naltrexone
Intervention MeSH terms: Naltrexone; Buprenorphine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Outpatient detoxification; Opioid dependence; Naltrexone; Vivitrol; Buprenorphine