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
  Purpose

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.

Condition Intervention Phase
Opiate-Related Disorders
Cocaine-Related Disorders
Drug: Methadone
Behavioral: Contingency Management
Drug: Methadone dose
Behavioral: Contingency Management/Noncontingent Incentives
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Abstinence from cocaine and heroin [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 300
Study Start Date: February 2004
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm One Behavioral: Contingency Management
Incentives given for cocaine abstinence
Drug: Methadone dose
flexible methadone dosing to 190 mg/day daily orally
Active Comparator: ArmTwo Drug: Methadone
100 mg/day orally
Behavioral: Contingency Management
Incentives given for cocaine abstinence
Behavioral: Contingency Management/Noncontingent Incentives
Incentives given independent of drug use
Active Comparator: Arm Three Drug: Methadone dose
flexible methadone dosing to 190 mg/day daily orally
Active Comparator: Arm Four Drug: Methadone
100 mg/day orally
Behavioral: Contingency Management/Noncontingent Incentives
Incentives given independent of drug use

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00292110

Locations
United States, Maryland
National Institute on Drug Abuse
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Investigators
Principal Investigator: Kenzie Preston, Ph.D. National Institute on Drug Abuse (NIDA)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute on Drug Abuse (NIDA) )
ClinicalTrials.gov Identifier: NCT00292110     History of Changes
Other Study ID Numbers: 999904390, 04-DA-N390
Study First Received: February 14, 2006
Last Updated: February 19, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
HIV
Opiate Substitution
Pharmacokinetics
ECG
Polydrug Abuse

Additional relevant MeSH terms:
Cocaine-Related Disorders
Substance-Related Disorders
Mental Disorders
Cocaine
Methadone
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Opioid
Analgesics
Antitussive Agents
Respiratory System Agents
Narcotics

ClinicalTrials.gov processed this record on July 29, 2014