Agonist Replacement Therapy for Cocaine Dependence

Cocaine Dependence Clinical Trial

Official title:

Agonist Replacement Therapy for Cocaine Dependence: Identifying Novel Medications

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00697138
• Other study ID #: DA021155
• Secondary ID: Agonists for Coc
• Status: Completed
• Phase: Phase 1
• First received: June 11, 2008
• Last updated: February 29, 2012
• Start date: June 2006
• Est. completion date: January 2012

Study information

• Verified date: February 2012
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cocaine Dependence
• Cocaine-Related Disorders

Intervention

Drug:
• d-Amphetamine; Atomoxetine
Dexedrine (0-60 mg/day); Strattera (0-80 mg/day)

Locations

Country	Name	City	State
United States	University of Kentucky Medical Center	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
University of Kentucky	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Behavioral effects of cocaine		Measure throughout the study	No
Secondary	Heart rate; blood pressure; ECG		Measure throughtout study	Yes