Substance-Related Disorders
Conditions
Keywords
cognitive-behavior therapy, d-cycloserine, cognitive enhancer, drug dependence, opiate dependence, exposure, isolated doses of d-cycloserine, isolated doses of matching pill placebo, DCS
Brief summary
This study examines whether isolated doses of d-cycloserine enhance the efficacy of an exposure-based cognitive-behavioral treatment for chronic and treatment refractory substance dependence.
Detailed description
This is a placebo-controlled trial of the efficacy of 50mg d-cycloserine or matching pill placebo for enhancing the efficacy of CBT.
Interventions
DRUGD-cycloserine
Single dosage of D-cycloserine is given prior to each of 6 sessions of CBT-IC treatment (sessions 5-10)
DRUGPlacebo
Single dosage of placebo is given prior to each of 6 sessions of CBT-IC treatment (sessions 5-10)
Sponsors
National Institute on Drug Abuse (NIDA)
Massachusetts General Hospital
Boston University Charles River Campus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
The primary selection criteria include women and men between the ages of 18 and 65 who: 1. Meet DSM-IV criteria for opiate dependence, 2. Maintain a stable dose of methadone for two weeks prior to recruitment and: * fail to achieve take-home status for methadone dosing during at least the first four months of methadone treatment, * test positive on at least two toxicology screens for illicit drugs during the month prior to recruitment * have never achieved two consecutive toxicology screens free of illicit substances since entering the current treatment episode. 3. Meet study criteria for chronic stress: * unemployment criteria, and * affective disorder criteria.
Exclusion criteria
1. Patients with significantly unstable or uncontrolled medical illness which may interfere with participation in treatment (e.g., patients likely to require hospitalization during the study period). 2. Patients with a psychotic or organic mental disorder according to DSM-IV criteria. 3. Patients receiving medication affecting methadone metabolism (e.g. rifampin). 4. Patients with uncontrolled bipolar disorder as evidenced by meeting current criteria for mania or hypomania or meeting criteria for rapid cycling in the last year (as indicated by structured questioning of all patients meeting criteria for bipolar disorder). 5. Patients unable to complete the informed consent or unable to understand study procedures in the informed consent process. 6. Pregnancy or current alcohol use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Positive Toxicology Swabs for Illicit Substances | Weekly assessments with summation over three time periods: baseline, treatment (week 12), and follow-up (week 18) | The primary outcome assessment for this study was the percentage of oral toxicology swabs that were positive of illicit substances. Participants completed these swabs at each assessment point, as well as at each study therapy session. Toxicology swabs were supervised by study staff and used oral specimen collection to screen for opiates, methadone, cocaine, benzodiazepines, amphetamines, THC, and barbiturates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Addiction Severity Index (ASI) Drug Use Composite Score | Baseline, Mid Treatment (week 6), End of Treatment (week 12), Follow-up 1 (week 15), Follow-up 2 (week 18) | For the drug use composite scores, each of 13 questions about drug use is divided by its maximum answer value and by the total number of questions in the composite. These individual items are then summed, so that possible total scores range from 0 to 1, with higher scores reflecting greater drug use problem severity. |
Countries
United States
Participant flow
Recruitment details
This pilot study was terminated due to inadequate recruitment. The primary reason was unwillingness to take a study drug (a parent study that did not require randomized drug was likely a factor in this decision).
Pre-assignment details
15 people consented to this study but 4 did not meet entry criteria and 1 was loss to follow-up before completing baseline evaluations. 10 participants were randomized and 5 dropped out before taking study drug.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Characteristics All participants who consented to be in the study | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Overall Study Characteristics |
|---|---|
| Age, Continuous | 40.7 years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Percentage of Positive Toxicology Swabs for Illicit Substances
The primary outcome assessment for this study was the percentage of oral toxicology swabs that were positive of illicit substances. Participants completed these swabs at each assessment point, as well as at each study therapy session. Toxicology swabs were supervised by study staff and used oral specimen collection to screen for opiates, methadone, cocaine, benzodiazepines, amphetamines, THC, and barbiturates.
Time frame: Weekly assessments with summation over three time periods: baseline, treatment (week 12), and follow-up (week 18)
Population: Toxicology swabs were obtained on all 10 randomized participants irrespective of taking study drug. At baseline all 10 had toxicology swabs, at treatment (week 12) 7 had toxicology swabs and at follow-up (week 18) 7 had toxicology swabs.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Randomized Participants | Percentage of Positive Toxicology Swabs for Illicit Substances | Baseline Period | 80.0 percentage of positive toxicology swabs | Standard Deviation 35 |
| All Randomized Participants | Percentage of Positive Toxicology Swabs for Illicit Substances | Treatment Period (week12) | 65.7 percentage of positive toxicology swabs | Standard Deviation 45.8 |
| All Randomized Participants | Percentage of Positive Toxicology Swabs for Illicit Substances | Follow-up Period (week 18) | 59.6 percentage of positive toxicology swabs | Standard Deviation 44.1 |
Secondary
Addiction Severity Index (ASI) Drug Use Composite Score
For the drug use composite scores, each of 13 questions about drug use is divided by its maximum answer value and by the total number of questions in the composite. These individual items are then summed, so that possible total scores range from 0 to 1, with higher scores reflecting greater drug use problem severity.
Time frame: Baseline, Mid Treatment (week 6), End of Treatment (week 12), Follow-up 1 (week 15), Follow-up 2 (week 18)
Population: All randomized participants were asked to complete the ASI irrespective of taking study drug. At least one ASI was completed by 8 of the 10 randomized participants. At baseline 8 completed the ASI and the number of participants at each subsequent time point varied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Randomized Participants | Addiction Severity Index (ASI) Drug Use Composite Score | Follow-Up 2 (week 18) | 0.18 units on a scale | Standard Deviation 0.18 |
| All Randomized Participants | Addiction Severity Index (ASI) Drug Use Composite Score | Baseline | 0.27 units on a scale | Standard Deviation 0.14 |
| All Randomized Participants | Addiction Severity Index (ASI) Drug Use Composite Score | Mid-Treatment (week 6) | 0.19 units on a scale | Standard Deviation 0.12 |
| All Randomized Participants | Addiction Severity Index (ASI) Drug Use Composite Score | Endpoint of Treatment (week 12) | 0.21 units on a scale | Standard Deviation 0.13 |
| All Randomized Participants | Addiction Severity Index (ASI) Drug Use Composite Score | Follow-Up 1 (week 15) | 0.30 units on a scale | Standard Deviation 0.06 |