Aripiprazole for Prevention of Relapse to Cocaine Use in Methadone-Maintenance Patients
Condition: Cocaine Dependence; Cocaine-Related Disorders; Opioid-Related Disorders
MeSH terms: Recurrence; Cocaine-Related Disorders; Opioid-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  The effectiveness of methadone maintenance for treatment of heroin addiction has been
           well established. However, patients maintained on methadone may relapse to cocaine use,
           even when they are enrolled in a comprehensive treatment program. Relapse has been
           attributed to several factors, including drug-associated environmental stimuli.

        -  Aripiprazole is a drug used to treat schizophrenia and bipolar disorder, but it may have
           other uses. Research has shown that aripiprazole can reduce cocaine-seeking behavior in
           rats, and it has been investigated for use in treating amphetamine dependence. More
           research is needed to determine whether aripiprazole can prevent relapse to cocaine use
           in patients being treated with methadone.

      Objectives:

      - To determine whether aripiprazole prevents relapse to cocaine use more effectively than
      placebo in cocaine-abstinent patients maintained on methadone.

      Eligibility:

      - Individuals between 18 and 60 years of age who are current cocaine users seeking methadone
      treatment.

      Design:

        -  The study will last up to 41 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 methadone over the first 14 days of the study.

        -  Weeks 1 14: Participants will receive vouchers for regular cocaine-free urine samples.
           Those who successfully complete this phase will continue to the next part of the study.

        -  Weeks 13 27: Participants will receive either aripiprazole or placebo along with their
           methadone. During this part of the study, participants will keep electronic diaries to
           record cocaine use or craving and to record data on mood and activity.

        -  Weeks 28 33: Participants will stop taking the aripiprazole or placebo, but will
           continue the methadone treatment. Participants will continue to use the electronic
           diaries.

        -  Weeks 34 41: Participants will have the choice of transferring to a community clinic or
           gradually reducing doses of methadone 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 methadone effectively treats opioid dependence in polydrug users, some
      abstinent patients relapse to maladaptive use of cocaine during treatment. Relapse may be
      triggered by cocaine-associated cues. Work in a rodent relapse model has demonstrated that
      the atypical neuroleptic drug aripiprazole (Abilify), a partial agonist at dopamine D2
      receptors, can block relapse to cocaine use induced by cocaine-associated environmental
      stimuli or by priming doses of cocaine.

      Scientific goals. To determine whether aripiprazole prevents relapse to cocaine use more
      effectively than placebo in cocaine-abstinent patients maintained on methadone.

      Participant population. A total of up to 275 opioid-dependent outpatients abusing cocaine and
      opioids (110 evaluable) will be enrolled. Target enrollment will include 40% women and 60%
      minorities (mostly African-American).

      Experimental design and methods. The study will be a randomized double-blind clinical trial
      with two treatment groups (55 per group): aripiprazole (15 mg oral daily) and placebo. All
      patients will receive standard treatment (methadone daily and individual counseling weekly)
      for 39 weeks. To establish abstinence prior to aripiprazole induction, contingent vouchers
      will be given for each cocaine-negative urine specimen during the first 12 weeks (weeks
      1-12). Participants who are abstinent from cocaine during weeks 11 and 12 will be randomized
      to receive aripiprazole or aripiprazole placebo in weeks 13 through 27 (induction, weeks 13
      and 14; taper, week 27). From weeks 28-33, participants will receive methadone and counseling
      only, and then will be offered assistance to transfer to another program; those who do not
      transfer will undergo an 8-week methadone detoxification. The primary outcome measures will
      be time to relapse and longest duration of cocaine abstinence. Secondary objectives include
      evaluating whether the treatment groups differ in self-reported changes in drug use and
      proportion of drug-negative urine specimens. In addition, drug use, drug craving, stress, and
      HIV-risk behaviors such as injection practices will be assessed via electronic diaries
      (ecological momentary assessment, EMA).

      Benefits to participants and/or society. Participants will receive methadone, drug
      counseling, and contingency-management therapy. The methadone, counseling, and voucher
      interventions are likely to reduce participants use of heroin and cocaine and HIV risk
      behaviors. Aripiprazole may reduce the incidence of relapse to cocaine use.

      Risks to participants. Participants may experience side effects from aripiprazole and
      methadone and discomfort during withdrawal from methadone and aripiprazole. Methadone could
      raise serum levels of aripiprazole via inhibition of CYP2D6 metabolic pathways. The EMA
      component of the study may generate some assessment burden.
    

Intervention name(s): Airipiprazole; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Participants receive aripiprazole (orally, up to 15 mg/day) plus standard methadone maintenance (daily oral methadone and weekly individual counseling).; Participants receive identical capsules containing no active medication plus standard methadone maintenance (daily oral methadone and weekly individual counseling).
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Treatment
Keywords: Cocaine; Treatment; Airpiprazole; Methadone; Relapse; HIV; Ecological Momentary Assessment (EMA); Contingency Management