Cocaine Use Disorders
Conditions
Keywords
substance-related disorders
Brief summary
The purpose of this study is to explore the use of d-cycloserine (DCS) to facilitate extinction of response to cocaine cues in cocaine-dependent individuals, in hopes that it may lead to the development of new treatment options for cocaine dependence.
Detailed description
Cocaine dependence remains a serious problem in the United States 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 learning. D-cycloserine (DCS), a partial glutamate agonist, facilitates extinction of associative learning in animal models of fear-conditioning and clinical studies of exposure treatment for anxiety disorders. A recent study demonstrated DCS acceleration of extinction of cocaine-induced conditioned place preference in rats (Botreau et al., 2006). 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. In addition, to examine the neural substrates of extinction learning, a sub-set of individuals that are willing and eligible will undergo fMRI scanning procedures before and after the extinction protocol.
Interventions
50 mg d-cycloserine or placebo taken orally
DRUGPlacebo
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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 with the exceptions of nicotine and alcohol. Because of the high comorbidity of cocaine with alcohol and nicotine dependence, excluding nicotine and alcohol dependence would seriously compromise the feasibility of recruitment. Nicotine use immediately prior to the cue exposure/extinction session will be controlled. Although individuals who meet criteria for alcohol dependence will be accepted for study participation, anyone who has a measurable blood alcohol level on the day of the sessions will be excluded as acute alcohol intake can increase serum levels of DCS and lower the seizure threshold. 3. Use of one of the following methods of birth control by female subjects: birth control pills, 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 the research facility and have reliable transportation. 5. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) prior to the first session and through the final session. 6. Subjects must consent to random assignment to the DCS vs. placebo conditions. 7. For fMRI participants, subjects must be right-handed.
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 insulin-dependent diabetes, as these conditions may affect heart rate or skin conductance measurement. 3. 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. 4. Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) prior to and between the cue procedures. 5. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, alcohol or cocaine as appropriate) within the past 60 days. 6. Subjects currently taking B-blockers, anti-arrhythmic agents, psychostimulants or any other agents known to interfere with heart rate and skin conductance monitoring. 7. Known or suspected hypersensitivity to DCS. 8. Individuals taking medications that could adversely interact with study medications, including, but not limited to ethionamide, isoniazid, or amino acid supplements. 9. Subjects with a history of epilepsy or seizure disorder. 10. Subjects with significant liver impairment, as DCS may increase serum transaminases. 11. For fMRI participants, the need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications which could potentially interfere with fMRI. 12. For fMRI participants, clinically significant psychiatric or medical problems that would impair participation or limit ability to participate in scan.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Craving of Cocaine | two weeks | Average of participants' subjective measures of craving immediately following cue exposure at the one-week follow-up session. Participants rated craving on a 10 point analog scale ranging from 0 (not at all) to 10 (extremely). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DCS/DCS/DCS/Placebo Participants were assigned to receive 50 mg of DCS for each of 3 cue exposure sessions and a placebo at the one-week follow-up session.During cue exposure sessions, participants were asked to handle cocaine cues such as simulated crack, powder, and pipes while listening to an imagery script, and then they watched video footage of cocaine-related activities. | 10 |
| Placebo/Placebo/Placebo/Placebo Participants were assigned to receive a placebo for each of 3 cue exposure sessions and at the one-week follow-up session.During cue exposure sessions, participants were asked to handle cocaine cues such as simulated crack, powder, and pipes while listening to an imagery script, and then they watched video footage of cocaine-related activities. | 10 |
| DCS/ Placebo/DCS/Placebo Participants were assigned to receive 50 mg of DCS at the 1st and 3rd cue sessions and placebo at the 2nd cue session and the one-week follow-up session.During cue exposure sessions, participants were asked to handle cocaine cues such as simulated crack, powder, and pipes while listening to an imagery script, and then they watched video footage of cocaine-related activities. | 12 |
| DCS /DCS/Placebo Participants were assigned to receive 50 mg of DCS at 2 cue exposure sessions, and placebo at the one-week follow-up session. During cue exposure sessions, participants were asked to handle cocaine cues such as simulated crack, powder, and pipes while listening to an imagery script, and then they watched video footage of cocaine-related activities. Cue exposure was accompanied by instructions on how to cope with craving. | 23 |
| Placebo/Placebo/Placebo Participants were assigned to receive placebo at 2 cue expsosure sessions, and at the one-week follow-up session. Participants also received cognitive skills training.During cue exposure sessions, participants were asked to handle cocaine cues such as simulated crack, powder, and pipes while listening to an imagery script, and then they watched video footage of cocaine-related activities. Cue exposure was accompanied by instructions on how to cope with craving. | 24 |
| Total | 79 |
Baseline characteristics
| Characteristic | Total | DCS/DCS/DCS/Placebo | Placebo/Placebo/Placebo/Placebo | DCS/ Placebo/DCS/Placebo | DCS /DCS/Placebo | Placebo/Placebo/Placebo |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 10 Participants | 10 Participants | 12 Participants | 23 Participants | 24 Participants |
| Age, Continuous | 45.5 years STANDARD_DEVIATION 8.7 | 43.4 years STANDARD_DEVIATION 10.9 | 45.1 years STANDARD_DEVIATION 8.4 | 43.1 years STANDARD_DEVIATION 5.9 | 49.1 years STANDARD_DEVIATION 8.8 | 44.4 years STANDARD_DEVIATION 8.7 |
| Region of Enrollment United States | 79 participants | 10 participants | 10 participants | 12 participants | 23 participants | 24 participants |
| Sex: Female, Male Female | 17 Participants | 1 Participants | 4 Participants | 5 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 62 Participants | 9 Participants | 6 Participants | 7 Participants | 19 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 12 | 0 / 23 | 0 / 24 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 12 | 0 / 23 | 0 / 24 |
Outcome results
Primary
Subjective Craving of Cocaine
Average of participants' subjective measures of craving immediately following cue exposure at the one-week follow-up session. Participants rated craving on a 10 point analog scale ranging from 0 (not at all) to 10 (extremely).
Time frame: two weeks
Population: Data of participants who completed all cue exposure sessions and the one-week follow-up were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DCS Only | Subjective Craving of Cocaine | 2.47 units on a scale | Standard Deviation 2.39 |
| Placebo Only | Subjective Craving of Cocaine | 0.90 units on a scale | Standard Deviation 1.54 |
| DCS/ Placebo/DCS | Subjective Craving of Cocaine | 1.19 units on a scale | Standard Deviation 1.58 |
| DCS Plus Cognitive Skills Training | Subjective Craving of Cocaine | 1.06 units on a scale | Standard Deviation 1.23 |
| Placebo Plus Cognitive Skills Training | Subjective Craving of Cocaine | 1.69 units on a scale | Standard Deviation 2.24 |