Investigation of Cycloserine as a Smoking Cessation Treatment

Cycloserine Enhancement of Extinction Learning

Psychosocial treatments for drug abuse benefit some patients (Rawson et al 2004), but there is an urgent need for new treatment approaches that can improve treatment outcomes. One new approach involves facilitation of extinction of conditioned responses through the use of d-cycloserine, a partial agonist at the NMDA glycine site. This approach has proved useful for the treatment of several anxiety disorders. For example, treatment with d-cycloserine enhanced the efficacy of behavioral treatments for acrophobia (Ressler et al 2004) and social phobia (Hofmann et al 2006) by enhancing extinction of conditioned fear responses. This suggests that d-cycloserine has potential to enhance the efficacy of behavioral treatments for drug dependence by enhancing extinction of conditioned responses to drug cues. In this Phase I Cutting-Edge Basic Research Awards (CEBRA) application we propose a proof-of-concept study to examine effects of treatment with d-cycloserine for facilitating extinction of craving provoked by exposure to cigarette smoking cues. The benefits of this treatment approach together with cognitive behavioral treatment for reducing cigarette smoking will then be determined. Smoking cues will be presented using an established virtual reality simulator(Bordnick et al 2004; Bordnick et al 2005a)

Study Overview

• Status: Completed
• Conditions: Nicotine Addiction
• Intervention / Treatment: Drug: Placebo; Drug: Cycloserine

Detailed Description

See brief summary

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Want to participate in a treatment aimed at helping them stop smoking cigarettes
• Be English-speaking volunteers between 18-55 years of age
• Meet DSM-IV TR criteria for current nicotine dependence and smoke >10 cigarettes per day for the past year
• Meet DSM-IV TR criteria for cocaine dependence, but not seeking treatment for cocaine dependence at the time of study
• Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator

Exclusion Criteria:

• Meet DSM-IV TR criteria for abuse or dependence on alcohol or other drugs, except for nicotine and cocaine
• Have psychiatric disorders, such as: current major depression as assessed by SCID; lifetime history of schizophrenia, other psychotic illness, or bipolar illness as assessed by SCID; current organic brain disease or dementia assessed by clinical interview; history of or any current psychiatric disorder which would require ongoing treatment or which would make study compliance difficult; history of seizure disorder or severe head injury
• Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease
• Be pregnant or nursing. Female participants must either be unable to conceive (i.e., surgically sterilized, sterile, or post-menopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or spermicide). All females must provide negative pregnancy urine tests before study entry and at the end of study participation
• Have no history of adverse response to d-cycloserine
• Have any other illness, condition, or use of medications, which in the opinion of the P.I. and/or the admitting physician would preclude safe and/or successful completion of the study

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral administration of matching placebo pill on Days 1, 4, 7, and 10; Other Names: Sugar pill
Active Comparator: Cycloserine	Drug: Cycloserine; Oral administration of cycloserine medication (50 mg administered prior to each exposure treatment) on Day 1, 4, 7, and 10 of the study; Other Names: Seromycin; d-cycloserine

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

The effects of four weeks of single dose treatment with d-cycloserine or placebo on craving elicited by exposure to "virtual reality" smoking cues

The study will evaluate the effects of treatment with d-cycloserine (50mg administered prior to each exposure treatment) or placebo (n=20 per cell), on the efficacy exposure therapy using a virtual reality cue for smoking cessation when combined with cognitive behavioral therapy (CBT). Craving ratings will be assessed using standard questionnaires, which will be completed prior to and following virtual reality cue exposure. Smoking cessation and cocaine use will be assessed at three follow-up visits.

Secondary Outcome Measures

Outcome Measure	Measure Description
The effects of four weeks of single dose treatment with d-cycloserine or placebo, exposure to virtual reality smoking cues, and provision of manual-driven cognitive behavioral treatment on frequency of cigarette smoking and cocaine use	Study sessions will include assessment of urinary cocaine and breath CO, and participants will self-report cigarette smoking and cocaine use over the previous week. Smoking cessation and cocaine use will also be assessed at three follow-up visits.

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: February 3, 2010
• First Submitted That Met QC Criteria: February 3, 2010
• First Posted (Estimate): February 4, 2010

Study Record Updates

• Last Update Posted (Estimate): July 27, 2012
• Last Update Submitted That Met QC Criteria: July 25, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Smoking; Cycloserine; Nicotine
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; 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: H-23305; DPMC (Other Identifier: NIDA); R21DA023588 (U.S. NIH Grant/Contract)