Use of Donepezil for Treatment of Cocaine Dependence

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00467389
First received: April 27, 2007
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine the safety of intravenous cocaine in subjects receiving oral donepezil.


Condition Intervention Phase
Cocaine Abuse and Dependence
Drug: Donepezil, 5 mg daily
Other: Oral Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Donepezil Effects on Cocaine Craving and Pharmacokinetics

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Cocaine Safety in Subjects Receiving Donepezil [ Time Frame: Two weeks ] [ Designated as safety issue: Yes ]
    Patients evaluated for clinical and laboratory adverse events


Secondary Outcome Measures:
  • Cocaine Subjective Effects [ Time Frame: 3 to 30 minutes ] [ Designated as safety issue: No ]
    Cocaine Induced 'High' by VAS (visual analogue scale, between 3 and 30 minutes after intravenous dosing, in mm). VAS results ranged from 0 (minimum effect) to 100 (maximum effect).

  • Cocaine Pharmacokinetics [ Time Frame: 0 to 8 hours ] [ Designated as safety issue: No ]
    Area-Under-the-Curve for Plasma Concentration


Enrollment: 12
Study Start Date: February 2007
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Placebo First
Three days of daily treatment with oral placebo, followed by three days of daily treatment with 5 mg of donepezil
Drug: Donepezil, 5 mg daily
This is a commercially available cholinesterase inhibitor that is approved for use in Alzheimer's disease.
Other Name: Aricept
Other: Oral Placebo
Inactive Comparator with Similar Appearance to Active Medication
Other Name: Inactive Comparator
Experimental: Donepezil First
Three days of daily treatment with 5 mg of donepezil, followed by three days of daily treatment with oral placebo.
Drug: Donepezil, 5 mg daily
This is a commercially available cholinesterase inhibitor that is approved for use in Alzheimer's disease.
Other Name: Aricept
Other: Oral Placebo
Inactive Comparator with Similar Appearance to Active Medication
Other Name: Inactive Comparator

Detailed Description:

This is a randomized, double-blind, double-dummy, placebo controlled, inpatient, single-center, parallel group evaluation of the potential for oral donepezil to attenuate cocaine-induced craving. Non-treatment-seeking cocaine-experienced volunteers will receive baseline treatment with intravenous cocaine (30Mg). Forty-two subjects that tolerate baseline cocaine infusions will then receive two subsequent intravenous doses of cocaine during double-blind treatment with oral placebo or 5 mg daily of donepezil. Each dose of cocaine will be preceded or followed by administration of intravenous placebo (saline) in a random order.

  Eligibility

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

Inclusion Criteria:

  • Non-treatment seeking, experienced cocaine users, who have used cocaine by smoking or intravenous injection within the four weeks prior to screening, and must supply a cocaine-positive urine obtained within four weeks of entry into the study.

Exclusion Criteria:

  • Shows signs of psychostimulant toxicity, or has a history of a medical adverse reaction to cocaine or other psychostimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure.
  • Has a current psychiatric disorder other than drug abuse or dependence or dementia.
  • Meets the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for dependence to opiates, benzodiazepines, alcohol, or other sedative-hypnotics.
  • Has received opiate-substitution therapy (methadone or buprenorphine) within two months prior to enrollment.
  • Has current or past history of seizure disorder, including alcohol- or psychostimulant- related seizures, or family history of seizure disorder.
  • Has a diagnosis of adult asthma, or chronic obstructive pulmonary disease, including a history of acute asthma within the past two years, and those with current or recent (with the past two years) treatment with an inhaled or oral beta-adrenergic agonist.
  • Has had head trauma that resulted in neurological sequelae.
  • Has an unstable medical condition, which, in the judgement of investigators, would make participation hazardous.
  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: NCT00467389

Locations
United States, Missouri
VA Medical Center
Kansas City, Missouri, United States, 64128
Sponsors and Collaborators
Investigators
Principal Investigator: Kenneth Grasing, MD Department of Veterans Affairs
  More Information

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00467389     History of Changes
Other Study ID Numbers: NEUA-014-05S
Study First Received: April 27, 2007
Results First Received: December 18, 2013
Last Updated: May 21, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Acetylcholine
Acetylcholinesterase
Butyrylcholinesterase
Cholinesterase Inhibitor

Additional relevant MeSH terms:
Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Cholinesterase Inhibitors
Donepezil
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014