D-Cycloserine Facilitation of Cocaine - Cue Extinction
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Purpose
The purpose of this study is to explore the use of d-cycloserine 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Cocaine Use Disorders |
Drug: cycloserine |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | D-Cycloserine Facilitation of Cocaine - Cue Extinction |
- Subjective craving of cocaine [ Time Frame: two weeks ] [ Designated as safety issue: No ]
- physiological responses (heart rate, skin conductance) to cocaine cues [ Time Frame: two weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 80 |
| Study Start Date: | September 2008 |
| Estimated Study Completion Date: | April 2012 |
| Estimated Primary Completion Date: | April 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: 2
placebo
|
Drug: cycloserine
50 mg d-cycloserine or placebo taken orally
Other Name: seromycin
|
|
Experimental: 1
DCS
|
Drug: cycloserine
50 mg d-cycloserine or placebo taken orally
Other Name: seromycin
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
- Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
- 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.
- 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.
- Subjects must live within a 50-mile radius of the research facility and have reliable transportation.
- Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) prior to the first session and through the final session.
- Subjects must consent to random assignment to the DCS vs. placebo conditions.
- For fMRI participants, subjects must be right-handed.
Exclusion Criteria
- Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
- 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.
- 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.
- 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.
- Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, alcohol or cocaine as appropriate) within the past 60 days.
- Subjects currently taking B-blockers, anti-arrhythmic agents, psychostimulants or any other agents known to interfere with heart rate and skin conductance monitoring.
- Known or suspected hypersensitivity to DCS.
- Individuals taking medications that could adversely interact with study medications, including, but not limited to ethionamide, isoniazid, or amino acid supplements.
- Subjects with a history of epilepsy or seizure disorder.
- Subjects with significant liver impairment, as DCS may increase serum transaminases.
- For fMRI participants, the need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications which could potentially interfere with fMRI.
- For fMRI participants, clinically significant psychiatric or medical problems that would impair participation or limit ability to participate in scan.
Contacts and Locations| Contact: Lisa Nunn | 843-792-0476 | jenkinli@musc.edu |
| United States, South Carolina | |
| Medical University of South Carolina | Recruiting |
| Charleston, South Carolina, United States, 29425 | |
| Contact: Aimee McRae-Clark, Pharm.D. 843-792-5205 mcraeal@musc.edu | |
| Principal Investigator: Kathleen T Brady, MD, PhD | |
| Sub-Investigator: Therese Killeen, PhD | |
| Sub-Investigator: Megan M Moran-Santa Maria, PhD | |
| Sub-Investigator: Michael E Saladin, PhD | |
| Sub-Investigator: Karen Hartwell, MD | |
| Sub-Investigator: Bryan K Tolliver, MD, PhD | |
| Sub-Investigator: Robert Malcolm, MD | |
| Sub-Investigator: Aimee L McRae-Clark, Pharm D | |
| Behavioral Health Services of Pickens County | Active, not recruiting |
| Pickens, South Carolina, United States, 29671 | |
| Principal Investigator: | Kathleen T Brady, M.D., Ph.D. | Medical University of South Carolina |
More Information
No publications provided
| Responsible Party: | Kathleen T. Brady, M.D., Ph. D., Medical University of South Carolina |
| ClinicalTrials.gov Identifier: | NCT00759473 History of Changes |
| Other Study ID Numbers: | HRs#17972, 19784, R01DA023188, DPMCDA |
| Study First Received: | September 24, 2008 |
| Last Updated: | November 7, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Medical University of South Carolina:
|
substance-related disorders |
Additional relevant MeSH terms:
|
Substance-Related Disorders Mental Disorders Cycloserine Anti-Infective Agents, Urinary Anti-Infective Agents Therapeutic Uses Pharmacologic Actions |
Renal Agents Antibiotics, Antitubercular Anti-Bacterial Agents Antitubercular Agents Antimetabolites Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 23, 2013