Clinical trial NCT00467389: Use of Donepezil for Treatment of Cocaine Dependence
Official title: Donepezil Effects on Cocaine Craving and Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Abuse and Dependence
Keywords: Acetylcholine
Acetylcholinesterase
Butyrylcholinesterase
Cholinesterase Inhibitor
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2007-04-30
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: Cocaine Safety in Subjects Receiving Donepezil
timeFrame: Two weeks
Secondary outcomes:
measure: Cocaine Subjective Effects
timeFrame: 3 to 30 minutes
measure: Cocaine Pharmacokinetics
timeFrame: 0 to 8 hours
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: VA Medical Center
state: Missouri
Study officials:
affiliation: VA Medical Center
name: Kenneth Grasing, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/j.drugalcdep.2009.09.010.