Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management
Condition: Opiate-Related Disorders; Cocaine-Related Disorders
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - The treatment of addiction often hinges on preventing relapse into drug-using behaviors,
      which occurs at high rates even after prolonged abstinence. Some methadone patients continue
      to abuse cocaine and heroin during treatment, even with extensive psychosocial services. More
      research is needed to look at the results from earlier studies of continued drug use during
      methadone treatment, focusing on the results of fixed vs. flexible doses of methadone to
      reduce the likelihood of continued drug use and the role of monetary vouchers as an incentive
      to continue abstinence from illicit substances.

      Objectives:

      - To determine if the combination of flexible methadone dosing and voucher-based contingency
      management can improve rates of abstinence from heroin and cocaine.

      Eligibility:

      - Individuals between 18 and 65 years of age or older who are dependent on opioids (cocaine
      and/or heroin).

      Design:

        -  The study will last 40 weeks. After the initial screening, participants will receive
           daily methadone and weekly drug counseling sessions that will continue throughout the
           study.

        -  After 6 weeks of methadone treatment, participants who continue to use heroin and
           cocaine will be randomized to one of four groups for 16 weeks of study. Each group will
           receive a flexible or fixed dose of methadone, and one of two contingency management
           conditions.

        -  Flexible-dose participants will receive individualized dose increases, based on drug use
           and withdrawal. Fixed-dose participants will be set at a specific dose of methadone that
           will not be changed.

        -  The two contingency management conditions will be monetary vouchers given for regular
           cocaine-negative urine samples, or vouchers independent of urine cocaine screen results.

        -  After the study phase, participants will have 10 weeks of standard individual counseling
           and stable doses of methadone. Urine samples will continue to be collected, but no
           vouchers will be given.

        -  At the end of the study, participants will have the choice of transferring to a
           community clinic or undergoing a 10-week taper from methadone.
    

Detailed description: 
      Scientific goals. The primary goal is to determine if simultaneous abstinence from heroin and
      cocaine can be elicited by combining two approaches: flexible methadone dosing and
      voucher-based CM. Secondary goals include: 1) comparing saliva and plasma levels of
      methadone, cortisol, and prolactin as predictors of treatment outcome; and 2) evaluating the
      impact of methadone maintenance on renal function, lipid profile, and cardiac function.

      Methods. During an initial 6-week baseline phase, cocaine-abusing opioid-dependent outpatient
      participants (300 enrolled; 180 evaluable) will be stabilized on methadone 70 mg/day. At the
      end of baseline, participants who continue to use heroin and cocaine will be randomized to
      one of two dosing regimens and one of two CM conditions. In the flexible-dose regimen,
      participants will receive individualized dose increases (15 mg/day) to a maximum of 190 mg
      /day, based on heroin use and withdrawal. In the fixed-dose regimen, participants methadone
      dose will be increased to 100 mg/day and remain fixed there. Dose-group assignment will be
      double-blind: investigators will determine participants individualized dose increases, but
      only the pharmacists will know which participants actually receive them. The two CM
      conditions will be: vouchers contingent on cocaine-negative urine specimens, or noncontingent
      vouchers (i.e., vouchers independent of urine cocaine screen results). The main outcome
      measure will be the percentage of urines simultaneously negative for both cocaine and illicit
      opiates during treatment. For the concurrently run pharmacokinetic-pharmacodynamic portion,
      saliva and blood samples will be taken at regular intervals to determine levels of methadone,
      cortisol, and prolactin as predictors of treatment outcome. For the concurrently run
      medical-outcomes portion, urine (renal function), blood (lipid profile), and ECGs (cardiac
      function),will be obtained at set intervals.

      Hypothesis. Flexible methadone dosing and voucher-based CM will be safe and result in greater
      simultaneous abstinence from heroin and cocaine, higher treatment retention, and higher
      health-related QOL when compared to fixed methadone dosing and the absence of CM.

      Benefits. Participants will receive methadone, counseling, and some medical care at no
      charge. The methadone and voucher interventions are likely to reduce participants' use of
      heroin and cocaine. Counseling will include management of HIV risk behaviors. The study
      incorporates participant safety monitoring and will provide information relevant to improving
      the health and safety of community methadone-maintenance patients. The
      pharmacokinetic-pharmacodynamic part of the study does not benefit participants directly, but
      may lead to the development of more useful and less invasive drug-monitoring methods.

      Risks. Participants may experience side effects from methadone, discomfort during methadone
      withdrawal, and discomfort (or, rarely syncope) from blood draws.
    

Intervention name(s): Methadone; Contingency Management; Methadone dose; Contingency Management/Noncontingent Incentives
Intervention type(s): Drug; Behavioral; Drug; Behavioral
Intervention description(s): 100 mg/day orally; Incentives given for cocaine abstinence; flexible methadone dosing to 190 mg/day daily orally; Incentives given independent of drug use
Intervention MeSH terms: Methadone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: HIV; Opiate Substitution; Pharmacokinetics; ECG; Polydrug Abuse