Agonist Replacement Therapy for Cocaine Dependence

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Craig Rush, University of Kentucky
ClinicalTrials.gov Identifier:
NCT00697138
First received: June 11, 2008
Last updated: February 29, 2012
Last verified: February 2012
  Purpose

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 Intervention Phase
Cocaine Dependence
Drug: d-Amphetamine; Atomoxetine
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Behavioral effects of cocaine [ Time Frame: Measure throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Heart rate; blood pressure; ECG [ Time Frame: Measure throughtout study ] [ Designated as safety issue: Yes ]

Enrollment: 46
Study Start Date: June 2006
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: d-Amphetamine; Atomoxetine
Dexedrine (0-60 mg/day); Strattera (0-80 mg/day)

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697138

Locations
United States, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky, United States, 40536 0086
Sponsors and Collaborators
University of Kentucky
Investigators
Principal Investigator: Craig R Rush, Ph.D. University of Kentucky
  More Information

No publications provided

Responsible Party: Craig Rush, Princpal Investigator, University of Kentucky
ClinicalTrials.gov Identifier: NCT00697138     History of Changes
Other Study ID Numbers: DA021155, Agonists for Cocaine Abuse, R01DA021155, DPMC
Study First Received: June 11, 2008
Last Updated: February 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Kentucky:
Cocaine
Dependence
Pharmacotherapies

Additional relevant MeSH terms:
Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Cocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Vasoconstrictor Agents
Cardiovascular Agents
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014