Agonist Replacement Therapy for Cocaine Dependence
Cocaine dependence is a significant public health concern. The proposed research will provide important clinical information regarding the efficacy of agonists replacement therapies for managing cocaine dependence.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Basic Science
|Official Title:||Agonist Replacement Therapy for Cocaine Dependence: Identifying Novel Medications|
- Behavioral effects of cocaine [ Time Frame: Measure throughout the study ] [ Designated as safety issue: No ]
- Heart rate; blood pressure; ECG [ Time Frame: Measure throughtout study ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2006|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Drug: d-Amphetamine; Atomoxetine
Dexedrine (0-60 mg/day); Strattera (0-80 mg/day)
Cocaine abuse and dependence continue to be significant public health concerns. The number of Americans that used cocaine in the past month, the percentage of 12th-, 10th- and 8th-graders that used cocaine in the past year, and the percentage of treatment admissions involving cocaine has remained stable in recent years. In 1996, cocaine use cost society over $45 billion due to medical consequences, lost productivity and crime. Because of the public-health concerns and costs associated with its abuse, identifying a pharmacotherapy for cocaine dependence is a priority with the National Institute on Drug Abuse (N.I.D.A.). A pharmacological adjunct for cocaine dependence has not yet been identified.
The results of clinical trials suggest that agonist replacement therapies (e.g., d-amphetamine) may be effective for cocaine dependence. Because d-amphetamine reduces cocaine use, these clinical findings can be used as a reference to identify human laboratory procedures for screening putative pharmacotherapies. Identifying procedures for assessing the efficacy of putative pharmacotherapies is important because human laboratory studies can be conducted more rapidly and efficiently than clinical trials. The present project has two specific aims. The first specific aim is to demonstrate the sensitivity and predictive validity of human laboratory procedures commonly used to screen putative pharmacotherapies for cocaine dependence. To accomplish this aim, we will conduct two "proof-of-concept" studies. We will first demonstrate the safety and tolerability of d-amphetamine-cocaine combinations (Exp. 1). We will then demonstrate that d-amphetamine maintenance attenuates the reinforcing effects of cocaine (Exp. 2). The ability to attenuate the reinforcing effects of cocaine may be an important characteristic of an effective pharmacotherapy. The results of these studies will help elucidate the optimal conditions (e.g., dose) under which d-amphetamine might be expected to be effective. The second specific aim is to determine the efficacy of atomoxetine (Strattera®) as a putative agonist replacement pharmacotherapy for cocaine dependence. To accomplish this aim, we will conduct two experiments to determine the effects of cocaine during atomoxetine maintenance. We will first demonstrate the safety and tolerability of atomoxetine-cocaine combinations (Exp. 3). Finally, we will determine the reinforcing effects of intranasal cocaine during atomoxetine maintenance (Exp. 4). Atomoxetine, a potent norepinephrine uptake blocker, was chosen for study because its pharmacological and behavioral effects overlap to some extent with those of d-amphetamine, but it appears to have less abuse potential. Identifying novel agonist replacement therapies is important because clinicians may be reluctant to use d-amphetamine because of its abuse potential.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00697138
|United States, Kentucky|
|University of Kentucky Medical Center|
|Lexington, Kentucky, United States, 40536 0086|
|Principal Investigator:||Craig R Rush, Ph.D.||University of Kentucky|