Agonist Replacement Therapy for Cocaine Dependence
Information source: University of Kentucky
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cocaine Dependence
Intervention: d-Amphetamine; Atomoxetine (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: University of Kentucky Official(s) and/or principal investigator(s): Craig R Rush, Ph.D., Principal Investigator, Affiliation: University of Kentucky
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.
Clinical Details
Official title: Agonist Replacement Therapy for Cocaine Dependence: Identifying Novel Medications
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Basic Science
Primary outcome: Behavioral effects of cocaine
Secondary outcome: Heart rate; blood pressure; ECG
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
University of Kentucky Medical Center, Lexington, Kentucky 40536 0086, United States
Additional Information
Starting date: June 2006
Last updated: February 29, 2012
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