Cocaine Use Disorders
Conditions
Keywords
substance related disorders
Brief summary
In summary, this pilot study will explore the use of an innovative pharmacologic approach to the treatment of substance dependence through the facilitation of extinction of response to cocaine-conditioned cues in cocaine-dependent individuals. If DCS proves successful in this preliminary study, a controlled treatment trial will be planned. This novel approach could have implications for the treatment of multiple substance use disorders including methamphetamine, marijuana and opiate dependence.
Detailed description
Cocaine dependence remains a serious problem in the US today and in spite of two decades of intense research, efficacious pharmacotherapeutic treatments have not been identified. Cocaine-associated environmental cues can elicit drug craving and exposure to cocaine-related cues is likely to be involved in relapse. Emerging data supports the role of glutamate in extinction of associative learning in animal models of rear-conditioning and clinical studies of exposure treatment for anxiety disorders. A recent study demonstrated DCS acceleration of cocaine-induced conditioned place preference in rats. Exploration of DCS in facilitating extinction of response to drug-related cues in humans is needed. The proposed study will extend these innovative and promising findings from the basic science arena and anxiety disorders field in a proof of concept investigation of DCS facilitation of extinction of response to cocaine-related cues in a human laboratory paradigm.
Interventions
DRUGD-cycloserine
50 mg DCS
DRUGPlacebo
Placebo
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. 2. Subjects must meet DSM-IV criteria for current cocaine dependence. Subjects may meet criteria for abuse, but not dependence on any other substance within the past 60 days with the exception of nicotine. Because of the high comorbidity of cocaine and nicotine dependence, excluding nicotine dependence would seriously compromise the feasibility of recruitment. Nicotine use immediately prior to the testing session will be controlled. Alcohol has also been known to affect HPA function, however to enhance recruitment efforts individuals with alcohol dependence or abuse will be included in the study if they do not require medically supervised detoxification. 3. Use of one of the following methods of birth control by female subjects: barrier methods (diaphragm or condoms with spermicide or both), surgical sterilization, use of an intra-uterine contraceptive device, or complete abstinence from sexual intercourse. 4. Subjects must live within a 50-mile radius of our research program and have reliable transportation. 5. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine or alcohol) for 24 hours immediately prior to the GCRC admission. 6. Subjects must consent to random assignment to the DCS vs. placebo conditions.
Exclusion criteria
1. Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control. 2. Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect heart rate or skin conductance measurement. 3. Individuals with creatinine clearance of 1.2 or greater as DCS is renally excreted. 4. Subjects with a history of or current psychotic disorder, current major depressive disorder, bipolar affective disorder or a severe anxiety disorder as these may impact cue reactivity. 5. Subjects who are unwilling or unable to maintain abstinent from alcohol and other drugs of abuse (except nicotine) for 24 hours days prior to the cue procedure. 6. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine or cocaine as appropriate) within the past 60 days. 7. Subjects currently taking B-blockers, anti-arrythmic agents, psychostimulants or any other agents known to interfere with heart rate and skin conductance monitoring. 8. Known or suspected hypersensitivity to DCS. 9. Individuals taking medications that could adversely interact with study medications, including, but not limited to ethionamide, isoniazid, or amino acid supplements. 10. Subjects with a history of epilepsy or seizure disorder. 11. Subjects with significant liver impairment as DCS may increase serum transaminases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Craving Scale | Immediately following cue exposure | Scale assess cocaine craving following cocaine cue exposure after two administrations of DCS. Subjects rate craving on a scale from 0-10 with 0 indicating Not at all and 10 indicating Extremely. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D-cycloserine Participants received DCS prior to cocaine cue exposure sessions. | 12 |
| Placebo Participants received placebo prior to cocaine cue exposure sessions. | 15 |
| Total | 27 |
Baseline characteristics
| Characteristic | D-cycloserine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 15 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 10 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 15 |
| other Total, other adverse events | 0 / 12 | 0 / 15 |
| serious Total, serious adverse events | 0 / 12 | 0 / 15 |
Outcome results
Primary
Cocaine Craving Scale
Scale assess cocaine craving following cocaine cue exposure after two administrations of DCS. Subjects rate craving on a scale from 0-10 with 0 indicating Not at all and 10 indicating Extremely.
Time frame: Immediately following cue exposure
Population: Cocaine dependent individuals
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-cycloserine | Cocaine Craving Scale | 4.33 Units on a scale | Standard Deviation 3.98 |
| Placebo | Cocaine Craving Scale | 3.13 Units on a scale | Standard Deviation 2.92 |