Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Drug Abuse (NIDA) )
ClinicalTrials.gov Identifier:
NCT00292110
First received: February 14, 2006
Last updated: February 19, 2014
Last verified: August 2013

February 14, 2006
February 19, 2014
February 2004
August 2013   (final data collection date for primary outcome measure)
Abstinence from cocaine and heroin [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00292110 on ClinicalTrials.gov Archive Site
  • Time to relapse [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Psychological and psychosocial outcome [ Time Frame: 50 weeks ] [ Designated as safety issue: No ]
  • HIV Risk Behaviors [ Time Frame: 50 weeks ] [ Designated as safety issue: No ]
  • QT interval [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Urine microalbuminuria [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Blood lipid profile [ Time Frame: 50 weeks ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 50 weeks ] [ Designated as safety issue: No ]
  • Substance Dependence [ Time Frame: 50 weeks ] [ Designated as safety issue: No ]
  • Methadone plasma and saliva concentration [ Time Frame: 50 weeks ] [ Designated as safety issue: No ]
  • Cortisol and prolactin levels [ Time Frame: 50 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management
Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management

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.

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.

Interventional
Phase 1
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Opiate-Related Disorders
  • Cocaine-Related Disorders
  • Drug: Methadone
    100 mg/day orally
  • Behavioral: Contingency Management
    Incentives given for cocaine abstinence
  • Drug: Methadone dose
    flexible methadone dosing to 190 mg/day daily orally
  • Behavioral: Contingency Management/Noncontingent Incentives
    Incentives given independent of drug use
  • Experimental: Arm One
    Interventions:
    • Behavioral: Contingency Management
    • Drug: Methadone dose
  • Active Comparator: ArmTwo
    Interventions:
    • Drug: Methadone
    • Behavioral: Contingency Management
    • Behavioral: Contingency Management/Noncontingent Incentives
  • Active Comparator: Arm Three
    Intervention: Drug: Methadone dose
  • Active Comparator: Arm Four
    Interventions:
    • Drug: Methadone
    • Behavioral: Contingency Management/Noncontingent Incentives

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
300
August 2013
August 2013   (final data collection date for primary outcome measure)
  • INCLUSION CRITERIA:

    1. age between 18 and 65;
    2. physical dependence on opioids
    3. evidence of cocaine use, by urine screen and self-report
    4. able to attend methadone clinic 7 days/week

EXCLUSION CRITERIA:

  1. History of schizophrenia or any other DSM-IV psychotic disorder
  2. History of bipolar disorder
  3. Current Major Depressive Disorder;
  4. Current physical dependence on alcohol or sedative-hypnotics, e.g. benzodiazepines
  5. Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires (Shipley Institute of Living scale-estimated full-scale IQ less than 80)
  6. Medical illness that in the view of the investigators would compromise participation in research
  7. Urologic conditions that would inhibit urine collection
  8. Previous bowel obstruction.
  9. Previous history of the following: major abdominal surgery, major gynecologic / pelvic surgery, inflammatory bowel disease (Crohn s or ulcerative colitis), Meckel s diverticulum, congenital atresia or stenosis, diverticulitis, radiation enteropathy or stricture, bowel neoplasm, endometriosis, inguinal-femoral-umbilical-ventral hernia, volvulus, or neurogenic megacolon, frequent bezoars.
  10. Recent use of medications known to cause severe constipation.
  11. History of previous severe respiratory depression or coma due to methadone use.
  12. Pregnancy.
  13. Personal history of a serious arrhythmia such as ventricular tachycardia, ventricular fibrillation, or Torsade de pointes; personal history of congenital heart disease or arrhythmia.
  14. Personal history of congenital long QT syndrome (LQT).
  15. Family history of a congenital long QT syndrome.
  16. Family history of Torsade de pointes.
  17. Family history of sudden cardiac death below the age of forty years.
  18. Evidence of clinically significant structural heart disease.
  19. Personal history of severe electrolyte disorders.
  20. Recent use of anti-arrhythmic agents.
  21. Poor venous access.
  22. Lab values outside the parameters set in Table II. These exclusion values are based upon the Medical Screening guideline used previously at the NIDA-IRP.
  23. CD4 less than 200 or evidence of severely compromised immune system / AIDS
  24. Women who are able to get pregnant must agree to use a medically effective form of contraception while in the study.

Acceptable forms of contraception for this study include:

  1. Hormonal contraception (birth control pills, injected hormones, vaginal ring)
  2. Intrauterine device
  3. Barrier methods with spermicide (diaphragm with spermicide, condom with spermicide)
  4. Surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner)

Women who do not agree to use these medically effective forms of contraception while in the study will be excluded.

Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00292110
999904390, 04-DA-N390
Not Provided
National Institutes of Health Clinical Center (CC) ( National Institute on Drug Abuse (NIDA) )
National Institute on Drug Abuse (NIDA)
Not Provided
Principal Investigator: Kenzie Preston, Ph.D. National Institute on Drug Abuse (NIDA)
National Institutes of Health Clinical Center (CC)
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP