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Rivastigmine as a Treatment for Methamphetamine Dependence

Phase 1
Completed
Conditions
Methamphetamine Dependence
Substance Abuse
Methamphetamine Abuse
Interventions
Other: Placebo
Registration Number
NCT01073319
Lead Sponsor
Baylor College of Medicine
Brief Summary

To study the effects of treatment with rivastigmine on craving produced by experimental administration of methamphetamine.

Detailed Description

We recently completed a double-blind placebo-controlled human laboratory study demonstrating that treatment with a low dose of the acetylcholinesterase (AChE) inhibitor rivastigmine reduced methamphetamine (METH)-induced craving (see Preliminary Studies, Fig. 2). This finding is consistent with the preclinical report indicating that the AChE inhibitor donepezil reduced METH-seeking behavior in rats following exposure to a non-contingent dose of METH (Hiranita et al. 2006). To extend our clinical findings, we propose a 3-year human laboratory study to evaluate effects of higher doses of rivastigmine on METH-induced craving and on self-administration of METH. Our recently completed work indicates that 3mg rivastigmine attenuated METH-induced craving in the laboratory. Given that higher dosages of this produce greater inhibition of nicotinic acetylcholine (ACh) receptors (in the treatment of Alzheimer's disease), it is reasonable to predict that 6mg and 12mg will have more pronounced effects on craving and other measures of reinforcement. This human laboratory study is a critical next step in the evaluation of rivastigmine as a potential treatment for METH dependence. We propose to include only participants exhibiting METH-induced craving by screening potential participants prior to admission (criterion based upon Preliminary Studies, Fig. 5). Selection of participants demonstrating METH-induced craving will facilitate assessment of effects of rivastigmine on craving. The project has the following objectives:

Primary Objective: To characterize the effects of treatment with rivastigmine (0, 3, and 6 mg) on craving produced by experimental administration of METH (0, 15 and 30mg, IV).

Secondary Objective: To characterize the effects of treatment with rivastigmine (0, 3, and 6 mg) on choices for METH exhibited in a self-administration paradigm (0 and 5mg, IV).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
17
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboMatching oral placebo capsule as control.
Rivastigmine 3 mgRivastigmine-
Rivastigmine 6 mgRivastigmine-
Primary Outcome Measures
NameTimeMethod
Effects of rivastigmine and methamphetamine on cardiovascular measures

Beginning with intake, vital signs (temperature with orthostatic BP and HR) will be recorded every 8 hours. Before and after the intravenous METH infusion, subjects' physiologic responses will be closely monitored using repeated HR, BP, and ECG readings.

Secondary Outcome Measures
NameTimeMethod
Effects of rivastigmine and methamphetamine on subjective measures (craving and choices for METH)

Effects of treatment with rivastigmine on craving produced by experimental administration of METH (0, 15 and 30mg, IV) will be measured using a computerized visual analogue scale (VAS), designed to provide rapidly acquired ratings of METH-induced craving, dysphoria, and euphoria. VAS measures will be collected prior to METH administration and at 5, 10, 15, 20, 30, 45, 60, 90, and 120 min following METH administration. Effects of treatment with rivastigmine on choices for METH (0 and 5mg) will be assessed using an existing model of drug self-administration.

Trial Locations

Locations (1)

Michael E. DeBakey VA Medical Center

🇺🇸

Houston, Texas, United States

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