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

April 27, 2007
May 21, 2014
February 2007
September 2008   (final data collection date for primary outcome measure)
Cocaine Safety in Subjects Receiving Donepezil [ Time Frame: Two weeks ] [ Designated as safety issue: Yes ]
Patients evaluated for clinical and laboratory adverse events
The safety of cocaine administration in subjects receiving donepezil will be evaluated by electrocardiogram monitoring, self-reported adverse events, blood pressure, heart rate, 12-lead electrocardiograms, and safety laboratories. [ Time Frame: During dosing with intravenous cocaine, ECGs will be continuously monitored with a physician present. ]
Complete list of historical versions of study NCT00467389 on ClinicalTrials.gov Archive Site
  • 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
Plasma levels of cocaine and metabolites will be determined by liquid chromatography-tandem mass spectrometry after intravenous cocaine administration in placebo- and donepezil- treated subjects. Baseline and cocaine-induced increases in plasma HVA will [ Time Frame: Subjective effects of cocaine will be measured by VAS, BSCS, and the Multiple Choice Questionnaire. Additional psychometric measures will include the BSI, Beck Depression Inventory, POMS, and the Addiction Research Center Inventory. ]
Not Provided
Not Provided
 
Use of Donepezil for Treatment of Cocaine Dependence
Donepezil Effects on Cocaine Craving and Pharmacokinetics

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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Cocaine Abuse and Dependence
  • 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: Oral Placebo First
    Three days of daily treatment with oral placebo, followed by three days of daily treatment with 5 mg of donepezil
    Interventions:
    • Drug: Donepezil, 5 mg daily
    • Other: Oral Placebo
  • Experimental: Donepezil First
    Three days of daily treatment with 5 mg of donepezil, followed by three days of daily treatment with oral placebo.
    Interventions:
    • Drug: Donepezil, 5 mg daily
    • Other: Oral Placebo
Grasing K, Mathur D, Newton TF, DeSouza C. Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals. Drug Alcohol Depend. 2010 Feb 1;107(1):69-75.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
September 2008
September 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00467389
NEUA-014-05S
Yes
Department of Veterans Affairs
Department of Veterans Affairs
Not Provided
Principal Investigator: Kenneth Grasing, MD Department of Veterans Affairs
Department of Veterans Affairs
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP