Topiramate-Phentermine Combinations for Cocaine Dependence

Study Overview
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Brief Summary
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This study will determine the influence of topiramate (Topamax®) and phentermine (Adipex®), alone and in combination, on the reinforcing, subjective and physiological effects of cocaine.

Official Title
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Topiramate-Phentermine Combinations for Cocaine Dependence

Conditions
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Cocaine Use Disorder

Intervention / Treatment
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* Drug: Cocaine
* Drug: Placebo
* Drug: Phentermine
* Drug: Topiramate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recent cocaine use by the intranasal or intravenous route Exclusion Criteria: Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation Females not currently using effective birth control Contraindications to cocaine, topiramate or phentermine

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects will be maintained on oral placebo. Subjects will be maintained on placebo and phentermine during placebo maintenance. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance. | Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and topiramate.<br>Drug: Placebo<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and topiramate.<br>Drug: Phentermine<br>* The pharmacodynamic effects of phentermine maintenance will be determined during maintenance on placebo and topiramate.<br>* Other names: Adipex®;|
| Experimental: Topiramate Dose 1<br>Subjects will be maintained on the low topiramate dose. Subjects will be maintained on placebo and phentermine during maintenance on the low dose of topiramate. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance. | Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and topiramate.<br>Drug: Placebo<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and topiramate.<br>Drug: Phentermine<br>* The pharmacodynamic effects of phentermine maintenance will be determined during maintenance on placebo and topiramate.<br>* Other names: Adipex®;Drug: Topiramate<br>* The pharmacodynamic effects of chronic topiramate will be determined.<br>* Other names: Topamax®;|
| Experimental: Topiramate Dose 2<br>Subjects will be maintained on the high topiramate dose. Subjects will be maintained on placebo and phentermine during maintenance on the high dose of topiramate. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance. | Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and topiramate.<br>Drug: Placebo<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and topiramate.<br>Drug: Phentermine<br>* The pharmacodynamic effects of phentermine maintenance will be determined during maintenance on placebo and topiramate.<br>* Other names: Adipex®;Drug: Topiramate<br>* The pharmacodynamic effects of chronic topiramate will be determined.<br>* Other names: Topamax®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reinforcing Effects | The reinforcing effects of cocaine will be determined using a self-administration procedure in which subjects choose to take previously sampled doses. | Nine times over approximately five weeks inpatient admission. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective effects | Subjects will complete subjective effects measures during nine sessions while they are admitted to our inpatient unit. These items will ask about drug effects and general mood. | Nine times over approximately five weeks inpatient admission. | 
| Physiological Effects | Physiological measures will be completed daily while subjects are admitted to our inpatient unit. Physiological measures include temperature, heart rate and blood pressure. | Daily over approximately five week inpatient admissions | 
| Side effects | Subjects will complete a side effects questionnaire daily while they reside on the inpatient unit. Side Effects questions will query subjects about common effects of centrally active medications. | Daily over approximately five weeks of inpatient admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cocaine, Pharmacotherapy, Phentermine, Topiramate, Self-Administration