Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients
Condition: Opioid-Related Disorders
MeSH terms: Recurrence; Opioid-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Though the drug buprenorphine effectively treats dependence on opioids like heroin, some
           abstinent patients relapse to use during treatment. This relapse may be triggered by
           stress or stressful situations, and buprenorphine probably has no specific protective
           effect in these situations. Buprenorphine probably also has no specific effect on
           relapse to cocaine use.

        -  Research has shown that clonidine, a drug originally prescribed to treat high blood
           pressure and some symptoms of opioid withdrawal, can help block stress-induced relapse
           to heroin and cocaine seeking in rats. Researchers are interested in studying whether a
           combination of clonidine and buprenorphine may be more effective in preventing drug
           relapse than administering one of the medications alone.

      Objectives:

      - To determine whether clonidine, given to abstinent patients maintained on buprenorphine, is
      more effective than placebo in preventing relapse to heroin or cocaine use.

      Eligibility:

      - Individuals between 18 and 50 years of age who are current cocaine or heroin users seeking
      treatment.

      Design:

        -  The study will last up to 36 weeks, with four phases of treatment and a follow-up
           evaluation. Three times a week, participants will be asked to report illicit drug use
           and provide urine and breath samples. Throughout the study, participants will receive
           individual counseling in weekly 40 60 minute sessions. Other samples and tests will be
           scheduled as required by the study researchers.

        -  Patients will be stabilized on daily buprenorphine over the first 14 days of the study.

        -  Weeks 1 8: Participants will receive vouchers for regular substance-free urine samples.
           Those who successfully complete this phase will continue to the next part of the study.

        -  Weeks 7 9: Participants will receive either clonidine or placebo along with the
           buprenorphine. The dose of clonidine will be stabilized during this time.

        -  Weeks 9 22: Participants will continue to receive either clonidine or placebo along with
           the buprenorphine. During this part of the study, participants will keep electronic
           diaries to record drug use or craving and to record data on mood, stress levels, and
           activity.

        -  Weeks 23 28: Participants will stop taking the clonidine or placebo, but will continue
           the buprenorphine treatment. Participants will continue to keep electronic diaries.

        -  Weeks 29 36: Participants will have the choice of transferring to a community clinic
           transfer or gradually reducing doses of buprenorphine to end the study.

        -  Participants will return for a follow-up visit and urine sample 6 months after the end
           of the study.
    

Detailed description: 
      Background. Though buprenorphine effectively treats opioid dependence, some abstinent
      patients relapse to maladaptive use of opioids during treatment. Relapse may be triggered by
      stress. Rodent studies have demonstrated that stress can induce relapse to heroin and cocaine
      use (Erb, et al., 1996; Shaham, et al., 1996; Shaham and Stewart, 1995). In a rodent model,
      stress-induced relapse to heroin and cocaine seeking is blocked by the alpha-2 adrenergic
      agonist clonidine. In this study, clonidine will be compared to placebo in preventing relapse
      to opioid abuse in opioid maintained patients who have achieved abstinence while on
      buprenorphine and contingency management.

      Scientific goals. To determine whether clonidine, given to abstinent patients maintained on
      buprenorphine, prevents relapse to opioid use more effectively than placebo.

      Participant population. 300 opioid-dependent outpatients (120 evaluable). Target enrollment
      will include 40 persent women and 60 percent minorities (mostly African-American).

      Experimental design and methods. The study will be a randomized double-blind clinical trial.
      Two treatment groups will be studied (60/group), one receiving clonidine and the other
      receiving placebo. Assignment to treatment group will be randomized. All patients will
      receive buprenorphine daily (8 mg to 24 mg SL) and individual counseling weekly throughout 28
      weeks of treatment. In order to establish abstinence prior to clonidine induction, after one
      week of stabilization on buprenorphine, they will receive contingent vouchers for
      opioid-negative urine specimens for 8 weeks (weeks 1-8). Patients who are abstinent from
      illicit opioids during weeks 5 and 6 will be randomized to receive clonidine (0.3 mg oral
      dose) or clonidine placebo from weeks 9 through 20. Participants who are not abstinent will
      be switched to methadone for four weeks (usual dose from 50 mg to 100 mg) followed by an
      eight week methadone taper. Assignment to clonidine or placebo will be double-blind. Weeks 21
      and 22 will include a clonidine taper to avoid rebound hypertension. From weeks 23-28,
      participants will receive buprenorphine and counseling only, and then will be offered
      assistance to transfer to another program; those who do not transfer will undergo an 8-week
      buprenorphine taper. The primary outcome measures will be longest duration of opioid
      abstinence, time to relapse, and the proportion of opioid-negative urine specimens over time
      during the Intervention phase. In addition, fluctuations in drug use, drug craving, stress,
      and HIV-risk behaviors such as injection drug use will be assessed via ecological momentary
      assessment (EMA).

      Benefits to participants and/or society. Participants will receive buprenorphine, drug
      counseling, and contingency-management therapy. The buprenorphine and voucher interventions
      are likely to reduce participants' use of opioids. Counseling will include reduction of HIV
      risk behaviors.

      Risks to participants. Participants may experience side effects from clonidine,
      buprenorphine, or methadone and discomfort during withdrawal from each drug. In particular,
      discontinuation of clonidine may cause rebound hypertension. The EMA component of the study
      may generate some assessment burden.
    

Intervention name(s): Clonidine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): clonidine up to 0.3 mg/day oral; oral capsules daily
Intervention MeSH terms: Clonidine
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Treatment
Keywords: Opioid Dependence; Clonidine; Buprenorphine; Opioid Abstinence; Relapse