Opiate-Related DisordersPhase 1NCT00292110
Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management
A Phase 1 study testing Methadone, Contingency Management and Methadone dose in people with Opiate-Related Disorders and Cocaine-Related Disorders, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opiate-Related Disorders, Cocaine-Related Disorders
- What is being tested?
- Methadone, Contingency Management and Methadone dose
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2004to 9 Aug 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age between 18 and 65;
- physical dependence on opioids
- evidence of cocaine use, by urine screen and self-report
- able to attend methadone clinic 7 days/week
Who cannot join
- History of schizophrenia or any other DSM-IV psychotic disorder
- History of bipolar disorder
- Current Major Depressive Disorder;
- Current physical dependence on alcohol or sedative-hypnotics, e.g. benzodiazepines
- 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)
- Medical illness that in the view of the investigators would compromise participation in research
Show all 30Show fewer
- Urologic conditions that would inhibit urine collection
- Previous bowel obstruction.
- 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.
- Recent use of medications known to cause severe constipation.
- History of previous severe respiratory depression or coma due to methadone use.
- Pregnancy.
- Personal history of a serious arrhythmia such as ventricular tachycardia, ventricular fibrillation, or Torsade de pointes; personal history of congenital heart disease or arrhythmia.
- Personal history of congenital long QT syndrome (LQT).
- Family history of a congenital long QT syndrome.
- Family history of Torsade de pointes.
- Family history of sudden cardiac death below the age of forty years.
- Evidence of clinically significant structural heart disease.
- Personal history of severe electrolyte disorders.
- Recent use of anti-arrhythmic agents.
- Poor venous access.
- 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.
- CD4 less than 200 or evidence of severely compromised immune system / AIDS
- 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:
- Hormonal contraception (birth control pills, injected hormones, vaginal ring)
- Intrauterine device
- Barrier methods with spermicide (diaphragm with spermicide, condom with spermicide)
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute on Drug Abuse
Baltimore, Maryland, 21224
About this study
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.
Read more
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.
Read the 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.
- Being tested
- Methadone, Contingency Management, Methadone dose, Contingency Management/Noncontingent Incentives
- Keywords
- HIV, Opiate Substitution, Pharmacokinetics, ECG, Polydrug Abuse
- Medical subject headings
- Cocaine-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
100 mg/day orally
Contingency ManagementBehavioural
Incentives given for cocaine abstinence
Methadone doseDrug
flexible methadone dosing to 190 mg/day daily orally
Contingency Management/Noncontingent IncentivesBehavioural
Incentives given independent of drug use
| Study group | Role | What they receive |
|---|---|---|
| Arm Four | Active comparator | Not described Receives: Drug: Methadone; Behavioral: Contingency Management/Noncontingent Incentives |
| Arm One | Experimental | Not described Receives: Behavioral: Contingency Management; Drug: Methadone dose |
| Arm Three | Active comparator | Not described Receives: Drug: Methadone dose |
| ArmTwo | Active comparator | Not described Receives: Drug: Methadone; Behavioral: Contingency Management; Behavioral: Contingency Management/Noncontingent Incentives |
What is being measured
The primary outcome is the main question the study is designed to answer.
Abstinence from cocaine and heroin
Measured: 16 weeks
Secondary outcomes (10)
Time to relapse
Measured: 24 weeks
Psychological and psychosocial outcome
Measured: 50 weeks
HIV Risk Behaviors
Measured: 50 weeks
QT interval
Measured: 24 weeks
Urine microalbuminuria
Measured: 24 weeks
Blood lipid profile
Measured: 50 weeks
Quality of life
Measured: 50 weeks
Substance Dependence
Measured: 50 weeks
Methadone plasma and saliva concentration
Measured: 50 weeks
Cortisol and prolactin levels
Measured: 50 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2006 (estimated)
- Study start1 Feb 2004
- Primary completion9 Aug 2013
- Study completion9 Aug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Opiate-Related DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kenzie Preston, Ph.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00292110
- Sponsor's protocol ID
- 999904390
- Other IDs
- 04-DA-N390
- Status last verified
- 9 Aug 2013
- First submitted
- 14 Feb 2006
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Ball JC, Lange WR, Myers CP, Friedman SR. Reducing the risk of AIDS through methadone maintenance treatment. J Health Soc Behav. 1988 Sep;29(3):214-26. No abstract available.
PubMed 3241064Barthwell A, Senay E, Marks R, White R. Patients successfully maintained with methadone escaped human immunodeficiency virus infection. Arch Gen Psychiatry. 1989 Oct;46(10):957-8. doi: 10.1001/archpsyc.1989.01810100099020. No abstract available.
PubMed 2802930Belding MA, McLellan AT, Zanis DA, Incmikoski R. Characterizing "nonresponsive" methadone patients. J Subst Abuse Treat. 1998 Nov-Dec;15(6):485-92. doi: 10.1016/s0740-5472(97)00292-4.
PubMed 9845861
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management
- ClinicalTrials.gov ID
- NCT00292110
- Acronym / sponsor ID
- 999904390
- Keywords
- HIV, Opiate Substitution, Pharmacokinetics, ECG, Polydrug Abuse
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 1 Feb 2004
- Primary completion
- 9 Aug 2013 (actual)
- Study completion
- 9 Aug 2013 (actual)
- First posted
- 15 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm Four | Active comparator | Drug: Methadone, Behavioral: Contingency Management/Noncontingent Incentives |
| Arm One | Experimental | Behavioral: Contingency Management, Drug: Methadone dose |
| Arm Three | Active comparator | Drug: Methadone dose |
| ArmTwo | Active comparator | Drug: Methadone, Behavioral: Contingency Management, Behavioral: Contingency Management/Noncontingent Incentives |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
Key exclusion criteria (30 listed)
- History of schizophrenia or any other DSM-IV psychotic disorder
- History of bipolar disorder
- Current Major Depressive Disorder;
- Current physical dependence on alcohol or sedative-hypnotics, e.g. benzodiazepines
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methadone100 mg/day orally | Drug | Arm Four, ArmTwo |
| Contingency ManagementIncentives given for cocaine abstinence | Behavioural | Arm One, ArmTwo |
| Methadone doseflexible methadone dosing to 190 mg/day daily orally | Drug | Arm One, Arm Three |
| Contingency Management/Noncontingent IncentivesIncentives given independent of drug use | Behavioural | Arm Four, ArmTwo |
Primary outcome
Abstinence from cocaine and heroin
Time frame: 16 weeks
10 secondary outcomes
Time to relapse
Time frame: 24 weeks
Psychological and psychosocial outcome
Time frame: 50 weeks
HIV Risk Behaviors
Time frame: 50 weeks
QT interval
Time frame: 24 weeks
Urine microalbuminuria
Time frame: 24 weeks
Blood lipid profile
Time frame: 50 weeks
Quality of life
Time frame: 50 weeks
Substance Dependence
Time frame: 50 weeks
Methadone plasma and saliva concentration
Time frame: 50 weeks
Cortisol and prolactin levels
Time frame: 50 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 3241064Ball JC, Lange WR, Myers CP, Friedman SR. Reducing the risk of AIDS through methadone maintenance treatment. J Health Soc Behav. 1988 Sep;29(3):214-26. No abstract available.
- Background: PubMed 2802930Barthwell A, Senay E, Marks R, White R. Patients successfully maintained with methadone escaped human immunodeficiency virus infection. Arch Gen Psychiatry. 1989 Oct;46(10):957-8. doi: 10.1001/archpsyc.1989.01810100099020. No abstract available.
- Background: PubMed 9845861Belding MA, McLellan AT, Zanis DA, Incmikoski R. Characterizing "nonresponsive" methadone patients. J Subst Abuse Treat. 1998 Nov-Dec;15(6):485-92. doi: 10.1016/s0740-5472(97)00292-4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenzie Preston, Ph.D. principal investigator
National Institute on Drug Abuse (NIDA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methadone, Contingency Management and Methadone dose in people with Opiate-Related Disorders and Cocaine-Related Disorders, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Abstinence from cocaine and heroin (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00292110, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.