Modafinil - Escitalopram Study for Cocaine Dependence
Drug: Modafinil and Escitalopram
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
|Official Title:||Combination Therapy With Modafinil and Escitalopram for the Treatment of Cocaine Dependence|
- The effects of modafinil and/or escitalopram and cocaine on cardiovascular measures [ Designated as safety issue: Yes ]Before and after each cocaine infusion, physiologic responses will be closely monitored using repeated HR, BP, and ECG readings. To evaluate safety, a DSMB will meet annually and following any serious AE to examine data as well as any new published information on modafinil and/or escitalopram relevant to the project. The number of AEs (including arrhythmias and ECG changes), changes in BP and HR, changes in cocaine PKs, and changes in mood and psychiatric symptoms (using the BSI, BDI, POMS, and BPRS) will also be assessed throughout the study.
- The effects of modafinil and/or escitalopram and cocaine on subjective measures [ Designated as safety issue: No ]The ability of modafinil and/or escitalopram, as compared to placebo, to reduce cocaine-induced craving will be measured by VAS and ARCI.
- The effects of modafinil and/or escitalopram on reinforcing effects produced by cocaine [ Designated as safety issue: No ]The ability of modafinil and/or escitalopram, as compared to placebo, to reduce reinforcing effects produced by cocaine will be measured by choices for cocaine vs. money in the self-administration assay.
|Study Start Date:||August 2010|
|Study Completion Date:||July 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
Matching oral placebo capsules as control (Treatment 1: Modafinil 0 + Escitalopram 0).
Other Name: Sugar pill
|Active Comparator: Modafinil 200 mg + Escitalopram 20 mg||
Drug: Modafinil and Escitalopram
Treatment 4: Modafinil 200 mg + Escitalopram 20 mg
|Active Comparator: Modafinil 200 mg||
Treatment 2: Modafinil 200 mg + Escitalopram 0.
Other Name: Provigil
|Active Comparator: Escitalopram 20 mg||
Treatment 3: Modafinil 0 + Escitalopram 20 mg.
Other Name: Lexapro
In this application, we propose an augmentation strategy intended to improve the efficacy of modafinil as a potential treatment for cocaine dependence. Recent data indicates that during chronic treatment modafinil produces substantial dopamine transporter (DAT) inhibition. Given that cocaine inhibits DA, norepenepherine (NE) and serotonin (5-HT) reuptake, it is highly likely that targeting more than one neurotransmitter system will be necessary for a medication to be effective. Assuming that this statement is true, we hypothesize that a combination pharmacotherapeutic approach that concurrently modulates multiple neurotransmitter systems will likely demonstrate a clinically significant level of efficacy above trials in which a single medication is used. The proposed approach is based on preclinical data indicating that medications that increase brain 5-HT levels reduce the effects of stimulants. We hypothesize that combining modafinil with a selective serotonin reuptake inhibitor (SSRI), which will increase synaptic levels of 5-HT, will further improve the efficacy of modafinil for reducing the effects produced by cocaine.
Specific Aims: 1) to determine the effects of treatment with oral modafinil (0 or 200 mg) plus the SSRI escitalopram (0 or 20 mg) on the subjective and reinforcing effects produced by intravenous cocaine (0 and 20 mg) in the laboratory. 2) to characterize the cocaine dependent population and the genetic basis for the rewarding effects produced by cocaine. 3) to characterize the effect of both modafinil treatment and cocaine exposure onBrain Derived Neurotrophic Factor (BDNF) in plasma. We hypothesize that both modafinil treatment and cocaine exposure will alter plasma levels of BDNF. 4 a) provide a more frequent measure of heart rate (15 sec vs. 5 minutes) and b) measure a new dependent variable, physical activity, on days with and without cocaine exposure.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01601730
|United States, Texas|
|Michael E. DeBakey VA Medical Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Richard De La Garza, Ph.D.||Baylor College of Medicine|