D-Cycloserine Facilitation of Cocaine - Cue Extinction

March 14, 2016 updated by: Kathleen Brady, MD, PhD, Medical University of South Carolina
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

79

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Pickens, South Carolina, United States, 29671
        • Behavioral Health Services of Pickens County

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo/Placebo/Placebo/Placebo
Participants were assigned to receive 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.
Drug: Placebo
EXPERIMENTAL: DCS/DCS/DCS/Placebo
Participants were assigned to receive 50 mg of d-cycloserine (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.
Drug: D-Cycloserine (DCS)
50 mg d-cycloserine or placebo taken orally
Other Names:
  • seromycin
OTHER: DCS/Placebo/DCS/Placebo
Participants were assigned to receive 50 mg of d-cycloserine (DCS) at the first and third cue exposure sessions and a placebo at the second cue exposure 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.
Drug: D-Cycloserine (DCS)
50 mg d-cycloserine or placebo taken orally
Other Names:
  • seromycin
EXPERIMENTAL: DCS/DCS/Placebo
Participants were assigned to receive 50 mg of d-cycloserine (DCS) for each of 2 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. Cue exposure sessions were accompanied by instructions on coping with craving.
Drug: D-Cycloserine (DCS)
50 mg d-cycloserine or placebo taken orally
Other Names:
  • seromycin
ACTIVE_COMPARATOR: Placebo/Placebo/Placebo
Participants were assigned to placebo for each of 2 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. Cue exposure sessions were accompanied by instructions on coping with craving.
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective Craving of Cocaine
Time Frame: 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).
two weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of South Carolina

Collaborators

National Institute on Drug Abuse (NIDA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (ACTUAL)

October 1, 2011

Study Completion (ACTUAL)

October 1, 2011

Study Registration Dates

First Submitted

September 24, 2008

First Submitted That Met QC Criteria

September 24, 2008

First Posted (ESTIMATE)

September 25, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

April 13, 2016

Last Update Submitted That Met QC Criteria

March 14, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HRs#17972, 19784
  • R01DA023188 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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