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Agonist Replacement Therapy for Cocaine Dependence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00697138
Recruitment Status : Completed
First Posted : June 13, 2008
Last Update Posted : March 1, 2012
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Craig Rush, University of Kentucky

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cocaine Dependence Drug: d-Amphetamine; Atomoxetine Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Basic Science
Official Title: Agonist Replacement Therapy for Cocaine Dependence: Identifying Novel Medications
Study Start Date : June 2006
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Arm Intervention/treatment
Experimental: A Drug: d-Amphetamine; Atomoxetine
Dexedrine (0-60 mg/day); Strattera (0-80 mg/day)

Primary Outcome Measures :
  1. Behavioral effects of cocaine [ Time Frame: Measure throughout the study ]

Secondary Outcome Measures :
  1. Heart rate; blood pressure; ECG [ Time Frame: Measure throughtout study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Must meet diagnostic criteria for cocaine dependence Current cocaine use at study entry, as determined by urine screen Body Mass Index less or equal to 30 ECG results within normal limits If female, willing to use contraception throughout study

Exclusion Criteria:

Meets diagnostic criteria for dependence on drug other than cocaine and nicotine Currently seeking treatment for substance abuse Current or past history of serious illness including impaired heart function, seizures and central nervous system tumors Family history o heart disease or seizures Current of past psychiatric disorder other than substance abuse Pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00697138

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United States, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky, United States, 40536 0086
Sponsors and Collaborators
University of Kentucky
National Institute on Drug Abuse (NIDA)
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Principal Investigator: Craig R Rush, Ph.D. University of Kentucky

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Responsible Party: Craig Rush, Princpal Investigator, University of Kentucky Identifier: NCT00697138    
Other Study ID Numbers: DA021155
Agonists for Cocaine Abuse
R01DA021155 ( U.S. NIH Grant/Contract )
DPMC ( Other Identifier: NIDA )
First Posted: June 13, 2008    Key Record Dates
Last Update Posted: March 1, 2012
Last Verified: February 2012
Keywords provided by Craig Rush, University of Kentucky:
Additional relevant MeSH terms:
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Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Atomoxetine Hydrochloride
Anesthetics, Local
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Adrenergic Uptake Inhibitors
Adrenergic Agents
Central Nervous System Stimulants
Autonomic Agents