Clinical Trial: A Study of Neural Circuit Responses to Catechol-O-methyl Transferase (COMT) Inhibitors
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: A Randomized, Double-Blind Study of Neural Circuit Responses to COMT Inhibitors
Brief Summary: In this study, we seek to understand the effects of tolcapone and entacapone, FDA-approved COMT inhibitors, on reward choice and response inhibition, two measures we have previously shown to be altered in subjects with alcoholism. We now plan to test the hypothesis that COMT regulation of cortical dopamine levels is critical for regulation financial choices. Specifically, we propose that the lower levels of cortical dopamine present in individuals with the val158val COMT genotype reduces the inhibitory effect of frontal cortical areas on impulsive choice; an idea that extends previous hypotheses about the negative consequences of decreased prefrontal dopamine levels on inhibitory control. Moreover, this hypothesis suggests that inhibiting COMT may slow the degradation of dopamine and thereby decrease impulsivity.
Detailed Summary:
Drug consumption despite adverse consequences is a defining feature of human addiction (DSM-IV-TR, 2004). Impulsivity, a tendency to choose an immediate action despite delayed adverse consequences, is a major risk factor for tobacco, psychostimulant, opioid and alcohol abuse. In humans, impulsivity can be quantified by presenting subjects with a choice between a small immediate monetary reward or a larger but delayed reward. We recently found that the val158val allele for the enzyme catechol-O-methyltransferase (COMT), which is associated with more rapid cortical dopamine catabolism and thus lower cortical dopamine levels correlates with greater impulsivity and greater fMRI blood oxygen level dependent (BOLD) signal in dorsolateral prefrontal and posterior parietal cortices.
The first phase of the study will involve healthy controls. The second phase of the study will involve abstinent alcoholics matched for age, education, and gender. Subjects will range in age between 18 and 50 years old.
Sponsor: University of California, San Francisco
Current Primary Outcome: Behavioral tasks such as the delay discounting task, primary data, including the identity of each response and the associated reaction time will be stored and analyzed. [ Time Frame: 3 weeks ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Resting-state and task active fMRI data will be processed off-line using SPM2 and SPM5 software according to standard procedures for image slice-timing correction, realignment, normalization and smoothing. The functional data will be analyzed. [ Time Frame: 3 weeks ]
Original Secondary Outcome: Same as current
Information By: University of California, San Francisco
Dates:
Date Received: July 7, 2010
Date Started: March 2010
Date Completion: June 2019
Last Updated: April 12, 2016
Last Verified: April 2016
