Employment-based Reinforcement of Naltrexone Ingestion and Abstinence
Condition: Cocaine-Related Disorders; Heroin Dependence; Opioid-Related Disorders; Substance Abuse, Intravenous
MeSH terms: Substance-Related Disorders; Opioid-Related Disorders; Cocaine-Related Disorders; Heroin Dependence; Substance Abuse, Intravenous
Study type: Interventional

Summary: 
      A randomized study is planned over 5 years to evaluate the effectiveness of the Therapeutic
      Workplace in promoting naltrexone ingestion and abstinence in unemployed opiate-dependent
      injection drug users. Participants will be offered an opioid detoxification and naltrexone
      induction. Participants who complete the naltrexone induction will be randomly assigned to
      one of two groups. Both groups will be invited to work in the Therapeutic Workplace and
      prescribed naltrexone for 26 weeks. The groups will differ in the contingencies imposed to
      work and earn salary. Work Plus Naltrexone Contingency participants will be required to
      ingest naltrexone to work, and will receive a brief pay decrease for missing a dose. Work
      Plus Naltrexone Prescription participants will be prescribed naltrexone, but will not be
      required to ingest it to work. This study will provide a rigorous evaluation of a novel
      employment-based intervention, the Therapeutic Workplace, to promote naltrexone ingestion and
      drug abstinence in a population of injection drug users who are at considerable risk of
      spreading or contracting HIV infection. Hypotheses being tested in this study are: Naltrexone
      ingestion will be maintained in the group exposed to the employment-based naltrexone
      treatment significantly more than the group exposed to usual-care treatment package. Opiate
      abstinence will be maintained in the group exposed to the employment-based naltrexone
      treatment significantly more than the group exposed to usual-care treatment package.
    

Detailed description: 
      General Therapeutic Workplace Procedures The study was conducted in a model therapeutic
      workplace in which employment-based reinforcement contingencies are arranged to promote
      therapeutic behavior change. All participants were invited to attend the workplace for four
      hours every weekday to work on training programs that were almost fully automated.
      Participants earned vouchers that were exchangeable for goods and services in the community.
      Earnings were based on attendance in the workplace and performance in the training programs.
      Overall, voucher earnings were arranged such that participants could earn a base pay of
      $8.00/hour for the hours worked in the workplace plus approximately $2.00/hour for their
      performance on the training programs, for a total potential wage of $10/hour. Detailed
      descriptions of the therapeutic workplace, the web-based training programs, the staffing
      requirements, and the cost of the intervention can be found elsewhere. Participants in the
      Prescription group were eligible to work and earn vouchers independent of naltrexone
      consumption and/or drug use, however Contingency participants were only permitted to work
      when naltrexone consumption was objectively confirmed.

      Assessment Procedures Assessments were conducted at study intake and every 30 days throughout
      the study. Primary assessment measures included the Addiction Severity Index-Lite to evaluate
      changes in medical, employment, alcohol, drug, social, legal and psychological functioning;
      the opiate, cocaine, alcohol and nicotine sections of the Composite International Diagnostic
      Interview to evaluate psychiatric disorders; the Risk Assessment of Behavior to evaluate
      HIV-risk behaviors; and the Beck Depression Inventory-II and Symptom Checklist-90 to evaluate
      psychosocial functioning. Additional measures were collected.

      Naltrexone is contraindicated for patients with hepatic damage or reductions in liver
      functioning, and is rated in the FDA pregnancy category C. Therefore, blood samples were
      taken at intake, and months 1, 2, 3, and 5 for liver function (aminotransferase) levels, and
      pregnancy tests were conducted monthly. Naltrexone was discontinued permanently for one
      Contingency and one Prescription participant, and temporarily for one Contingency and one
      Prescription participant due to abnormal aminotransferase levels. Naltrexone was discontinued
      for one Contingency participant due to pregnancy.

      Urine samples were collected under same-sex staff observation upon arrival to the workplace
      every Monday, Wednesday, and Friday and at each 30-day assessment. Urine samples were
      analyzed immediately onsite for evidence of opiates (morphine, >300ng/ml), and cocaine
      (benzoylecgonine, >300ng/ml) using an Abbott AxSYM® fluorescent polarization immunoassay
      system. Samples collected at 30-day assessments were also analyzed for evidence of
      buprenorphine, methadone, amphetamine, benzodiazepines, and naltrexone. Urine samples were
      analyzed for naltrexone using an Enzyme Linked Immunosorbent Assay (ELISA) procedure; values
      <5ng/ml were considered negative for naltrexone (Friends Laboratory, MD). Participants were
      informed of their urinalysis results but there were no consequences for positive test
      results.

      Participants were instructed to notify study staff of any adverse events they experienced as
      soon as possible after the occurrence of the event. Any staff member who was notified by a
      participant of a potential adverse event filed a formal report into an automated system,
      which immediately distributed the reports to study investigators and key staff. Ongoing or
      unresolved adverse events were also included in a weekly adverse event report that was
      distributed to study investigators and key staff. At all 30-day assessments study staff
      assessed new adverse events and attempted to resolve any ongoing or unresolved adverse
      events. Participants were referred to medical staff to receive treatments and concomitant
      medications as needed, and reports were filed with the Institutional Review Board (IRB) and
      funding agency in accordance with the relevant institutional requirements and guidelines.

      Oral Naltrexone Treatment Participants were required to complete opiate detoxification before
      being invited to attend the therapeutic workplace for induction onto oral naltrexone
      (Depade®; Mallinckrodt Inc.). All opiate detoxification and naltrexone inductions were
      overseen by a physician and were guided solely by clinical considerations. All participants
      were notified of the potential for heightened risk of overdose in relation to naltrexone
      treatment and after extended periods of opiate abstinence. These notifications were issued by
      study staff during the study consent process, and at monthly assessments, and were issued by
      medical staff prior to initiating naltrexone treatment, and whenever a blood draw was
      conducted. Overdose risk reminders were read aloud and signed by the study participants.
      Finally, monthly lunch-time overdose prevention seminars were provided and free pizza was
      provided to encourage seminar attendance.

      During the 4-week induction period, participants were required to ingest scheduled doses of
      oral naltrexone to gain access to the therapeutic workplace. Induction onto oral naltrexone
      was determined by clinical judgment; participants were generally inducted using a 3-day dose
      run-up schedule (e.g., 12.5 mg, 25 mg, and 50 mg) in order to reach the full maintenance dose
      of 100 mg (Monday and Wednesday) and 150 mg (Friday) for the four-week period. Only
      participants who completed the induction period were considered eligible for randomization;
      these participants were invited to attend the therapeutic workplace for 26 weeks, and were
      offered oral naltrexone at no cost for the duration of the study. Participants were also
      offered access to outpatient drug abuse counseling that was provided independent of the
      workplace throughout their participation in the study.

      Randomization Prior to group assignment, participants were stratified to an experimental
      group in a 1:1 ratio according to whether they attended the workplace on >85% of days during
      the 4-week induction period, provided >1 opiate positive urine sample during the final 2
      weeks of the induction period, and provided >75% cocaine-positive urine samples during the
      4-week induction period. Eligible participants were assigned to one of two experimental
      groups (i.e., Prescription or Contingency) using an urn randomization method that ensured all
      levels of each stratification variable were evenly distributed across the groups. This
      research design originally proposed three experimental groups; therefore, four participants
      were randomized into a third experimental group that required participants to ingest
      naltrexone under staff observation and provide an opiate and cocaine-negative urine sample to
      maintain maximum pay in the workplace. Due to logistical difficulties encountered early in
      the study, it became clear that it would not be possible to randomize a sample size large
      enough to support a 3-group comparison within the planned study duration. A second power
      analysis was completed to determine the appropriate sample size for a 2-group comparison
      (described below) and the third experimental group was eliminated. Data from participants
      randomized into the third group have not been included in these analyses.

      Experimental Groups All participants were invited to attend the therapeutic workplace for 26
      weeks. Prescription group participants were provided a take-home supply of oral naltrexone
      every 30 days and were allowed to access the workplace independent of naltrexone ingestion.
      Contingency participants were required to ingest oral naltrexone under staff observation
      every Monday, Wednesday, and Friday to gain access to the workplace. Contingency participants
      who missed a naltrexone dose were not permitted to access the workplace until they were able
      to resume naltrexone. Additionally, missing a scheduled dose resulted in a base pay reset
      from $8 per hour to $1 per hour. After a reset a participant's base pay increased by $1 per
      hour to a maximum of $8 per hour for every day that a participant attended the workplace for
      at least 5 minutes.
    

Intervention name(s): employment-based reinforcement
Intervention type(s): Behavioral
Intervention description(s): Work Plus Naltrexone Contingency participants were required to ingest naltrexone to work, and received a brief pay decrease for missing a dose.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Behavior Therapy; Cocaine; Cocaine (IV); Cocaine Abuse; Cocaine Dependence; Contingency management; HIV risk behaviors; Heroin; Naltrexone; Opioid Dependence; sexual risk behaviors