Tacrine Effects on Cocaine Self-Administration and Pharmacokinetics
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First Received Date ICMJE | July 28, 2011 | ||||
Last Updated Date | May 4, 2012 | ||||
Start Date ICMJE | October 2012 | ||||
Estimated Primary Completion Date | September 2013 (final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Decreased cocaine-reinforced behavior [ Time Frame: Day 9 of treatment ] [ Designated as safety issue: No ] participants will make a series of choices between vouchers with an ascending monetary value and intravenous injections of cocaine |
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | Complete list of historical versions of study NCT01406522 on ClinicalTrials.gov Archive Site | ||||
Current Secondary Outcome Measures ICMJE |
Changes in cocaine pharmacokinetics [ Time Frame: Day 9 of treatment ] [ Designated as safety issue: No ] Plasma levels of cocaine and metabolites will be determined by liquid chromatography-tandem mass spectrometry |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Outcome Measures ICMJE | |||||
Original Other Outcome Measures ICMJE | |||||
Descriptive Information | |||||
Brief Title ICMJE | Tacrine Effects on Cocaine Self-Administration and Pharmacokinetics | ||||
Official Title ICMJE | Tacrine Effects on Cocaine Self-Administration and Pharmacokinetics | ||||
Brief Summary | No medications are currently available for treatment of psychostimulant addiction, a compulsive preoccupation with use of cocaine and related compounds. Tacrine, a medication that is currently prescribed for Alzheimer's disease, can decrease the amount of cocaine injections that laboratory animals choose to inject by vein. This project will determine if tacrine can also decrease cocaine-motivated behavior for human subjects in a laboratory setting. |
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Detailed Description | Background Reinforcing effects of cocaine are believed to arise through release of dopamine (DA) at the nucleus accumbens by neurons in the ventral tegmental area. Activation of cholinergic receptors on the cell bodies of these neurons can enhance DA release. Elevated levels of acetylcholine (ACh) in the nucleus accumbens may also serve to inhibit appetitive behaviors. Cholinesterase inhibitors such as tacrine increase synaptic levels of ACh by preventing its inactivation by acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE), and can improve learning and memory. In animals, cholinesterase inhibitors can attenuate cocaine self-administration and conditioned place preference. Tacrine is a centrally acting, reversible inhibitor of AChE and BuChE that is approved for treatment of Alzheimer's disease. In addition to its effects on the cholinergic system, tacrine can potentiate the actions of monoamines, including DA. Although use of tacrine has declined because of requirements for monitoring of potential liver toxicity and pharmacokinetics that necessitate multiple daily doses, it is more potent than other cholinesterase inhibitors in attenuating cocaine self-administration in animals. Pretreatment with tacrine can produce long-lasting reductions in cocaine-reinforced behavior in rats, described as persistent attenuation (cocaine self-administration is decreased by more than 80% over a period of three days during which no additional cholinesterase inhibitor is administered, see Figure 1). No previous studies have evaluated whether tacrine can modify the effects of cocaine in humans. Rationale To our knowledge, tacrine is the only compound that can produce persistent attenuation in rats treated with clinically relevant doses. If similar effects were observed in humans, this would lead to an important paradigm shift for substance abuse treatment, in that large reductions in cocaine-reinforced behavior could be produced without the need for continuous dosing with a medication. This scenario could remove the requirement for continued compliance with oral dosing in some patients with its associated potential for toxicity. Specific Aims:
Methods This is a randomized, double-blind, double-dummy, placebo-controlled, inpatient, single-center, parallel-group evaluation of the potential for oral tacrine to modify cocaine self-administration, cocaine-induced craving, and the pharmacokinetics of cocaine and tacrine. To evaluate the occurrence of persistent attenuation, the subjective and reinforcing effects of intravenous cocaine will be determined during oral treatment and three days following its discontinuation. |
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Study Type ICMJE | Interventional | ||||
Study Phase | Phase 2 | ||||
Study Design ICMJE | Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
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Condition ICMJE | Cocaine Dependence | ||||
Intervention ICMJE |
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Study Arm (s) |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Not yet recruiting | ||||
Estimated Enrollment ICMJE | 22 | ||||
Estimated Completion Date | November 2013 | ||||
Estimated Primary Completion Date | September 2013 (final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||
Ages | 21 Years to 50 Years | ||||
Accepts Healthy Volunteers | No | ||||
Contacts ICMJE |
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Location Countries ICMJE | United States | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT01406522 | ||||
Other Study ID Numbers ICMJE | R21DA029787 | ||||
Has Data Monitoring Committee | Yes | ||||
Responsible Party | KENNETH GRASING, Midwest Biomedical Research Foundation | ||||
Study Sponsor ICMJE | Midwest Biomedical Research Foundation | ||||
Collaborators ICMJE | |||||
Investigators ICMJE |
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Information Provided By | Midwest Biomedical Research Foundation | ||||
Verification Date | May 2012 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |