D-Cycloserine and Cue Exposure in Cocaine-Dependent Individuals

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.

Study Overview

• Status: Completed
• Conditions: Cocaine Use Disorders
• Intervention / Treatment: Drug: Placebo; Drug: D-cycloserine

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DCS; D-Cycloserine 50 mg is a partial glutamate agonist. Participants received DCS prior to cocaine cue exposure sessions.	Drug: D-cycloserine; 50 mg DCS
Placebo Comparator: Placebo; Saline comparator. Participants received placebo prior to cocaine cue exposure sessions.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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".	Immediately following cue exposure

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Aimee L McRae, Pharm.D., Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: October 23, 2008
• First Submitted That Met QC Criteria: October 24, 2008
• First Posted (Estimate): October 27, 2008

Study Record Updates

• Last Update Posted (Actual): July 6, 2018
• Last Update Submitted That Met QC Criteria: June 6, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: substance related disorders
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Cycloserine
• Other Study ID Numbers: HR#16454