Effectiveness of Topiramate in Treating Cocaine Dependent Individuals - 1

Study Overview
=================
Brief Summary
-----------------
Although a great amount of research has been conducted to resolve cocaine dependence, an effective treatment has yet to be discovered. Topiramate is a drug that was found to be useful in treating alcohol dependence. The purpose of this study is to determine the effectiveness of topiramate in treating cocaine dependent individuals.

Detailed Description
-----------------
Despite considerable scientific effort in the last two decades to develop treatment for cocaine dependent individuals, no medication has proven to be effective for treating cocaine dependence. Cocaine's rewarding effects are primarily a result of altering nerve pathways involving dopamine, a naturally-occurring chemical in the brain. Past research has focused on developing medications that either block dopamine or inhibit its release. However, these medications have not proven effective in treating cocaine dependence. This study will evaluate a new strategy of treating cocaine dependence by altering dopamine's functional expression. Dopamine-associated expression may be mediated through inhibition of gamma-aminobutyric acid (GABA), another brain chemical. Topiramate is a GABA inhibitor that has proven effective in treating alcohol dependent individuals. The purpose of this study is to determine the efficacy of topiramate in treating cocaine dependent individuals. Participants will be randomly assigned to receive either 300 mg per day of topiramate or placebo. In addition, participants will receive weekly cognitive behavioral therapy for 12 weeks. Follow-up visits will occur at 2 weeks and 1, 2, and 3 months following completion of treatment, and will include evaluations of cocaine use and psychosocial functioning.

Official Title
-----------------
Medication Development for Cocaine Dependence

Conditions
-----------------
Cocaine-Related Disorders

Intervention / Treatment
-----------------
* Drug: Topiramate + Cognitive Behavioral Therapy
* Drug: Placebo + Cognitive Behavioral Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Current DSM-IV diagnosis of cocaine dependence Good physical health as determined by a complete physical examination, an EKG within normal limits, and laboratory screening tests within acceptable parameters Seeking treatment for cocaine dependence At least one positive urine drug screen for cocaine at screen or baseline prior to randomization If female, a negative pregnancy test prior to study entry Agrees to use an effective method of contraception for the duration of the study Reads and writes English Willing to participate in behavioral treatment for cocaine dependence Exclusion Criteria: Current DSM-IV diagnosis of dependence on any psychoactive substance other than cocaine, alcohol, nicotine, caffeine, or marijuana Physiological dependence on alcohol and requires medical detoxification Neurological or psychiatric disorders Any Axis 1 disorder that warrants treatment or would preclude safe participation Organic brain disease Dementia Bulimia and/or anorexia nervosa Seizure disorders or epilepsy Any disorder which would require ongoing treatment or which would make study agent compliance difficult History of suicide attempts and/or current suicidal ideation, as determined by the SCID, within the 30 days prior to screening Serious medical illnesses Mandated by the court to obtain treatment for cocaine dependence Expected to relocate from the study area AIDS diagnosis HIV with a CD4 positive T cell count less than 500 mm Any subjects on any pharmacotherapy for the treatment of AIDS or HIV will be excluded Active syphilis that has not been treated, or refused treatment for syphilis Severe or life-threatening adverse reactions to medications (including topiramate) in the past or during this clinical trial Currently receiving active treatment with topiramate Use of a drug with known potential for toxicity to a major organ system (e.g., isoniazid, methotrexate), within 30 days prior to study entry Pregnant or breastfeeding Concurrent regular use of psychotropics, including but not limited to antidepressants, anxiolytics, antipsychotics, anticonvulsants, and psychomotor stimulant-type medications, St. John's Wort, yohimbine, ginko biloba, horehound, or any other central nervous system active herbal preparations Use of any opiate substitutes (e.g., methadone, levo-alpha acetyl methadol, buprenorphine), within the month prior to screening Clinically significant test results that, in the investigator's opinion, require immediate or urgent treatment Fever of unknown origin or neuroleptic malignant syndrome Serious medical co-morbidity requiring medical intervention or close supervision Received inpatient or outpatient treatment for cocaine dependence within the 4 weeks prior to study entry Past participation in a clinical trial utilizing topiramate Treatment with electroconvulsive therapy within the 3 months prior to study entry Member of the same household of an individual enrolled in the present study

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topiramate<br> | Drug: Topiramate + Cognitive Behavioral Therapy<br>* Topiramate up to 300 mg per day<br>* Other names: Topamax;|
| Placebo Comparator: Placebo<br> | Drug: Placebo + Cognitive Behavioral Therapy<br>* Placebo twice a day<br>* Other names: Sugar Pill;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of topiramate to reduce cocaine use(assessed by a combination of self-report of use and urine assays for benzoylecgonine, the major metabolite of cocaine). |  | Throughout the study (Visit 0 to Visit 12, and at 2 weeks, 1, 2, and 3 months following completion of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved psychosocial functioning; measured throughout the study, and at 2 weeks and 1, 2, and 3 months following completion of treatment |  | measured throughout the study, and at 2 weeks and 1, 2, and 3 months following completion of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cocaine addiction, cocaine dependence