Investigation of Cycloserine as a Smoking Cessation Treatment

Study Overview
=================
Brief Summary
-----------------
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)

Detailed Description
-----------------
See brief summary

Official Title
-----------------
Cycloserine Enhancement of Extinction Learning

Conditions
-----------------
Nicotine Addiction

Intervention / Treatment
-----------------
* Drug: Cycloserine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Time Frame |
| --- | --- | --- |
| 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. |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cycloserine, Nicotine, Smoking