Overview

This trial is active, not recruiting.

Condition impulsive behavior
Treatments tolcapone, placebo, entacapone
Sponsor University of California, San Francisco
Collaborator University of California, Berkeley
Start date March 2010
End date December 2015
Trial size 154 participants
Trial identifier NCT01158950, 2009-12-461, W81XWH-10-1-0231

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose basic science
Arm
(Experimental)
Drug: Tolcapone 200mg (single dose) administered at study visit
tolcapone Tasmar
Drug: Tolcapone 200mg (single dose) administered at study visit
(Placebo Comparator)
Drug: Placebo for tolcapone administered at study visit
placebo
Placebo (200mg) administered at study visit
(Experimental)
Drug: Entacapone 200mg (single dose) administered at study visit
entacapone Comtan
Entacapone 200mg (single dose) administered at study visit

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants from 18 years up to 50 years old.

Inclusion Criteria: - Age between 18 and 50 years. - Subject is right-handed. - If female, subject is non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device (IUD), hormonal birth control or barrier method). - Subject is able to read and speak English. - Subject is a high school graduate. - Subject is able and willing to provide written and informed consent. - Subject is able to understand and follow the instructions of the investigator, and understand all ratings scales. - Subject is in good health. Exclusion Criteria: - Using cocaine, stimulants (other than THC, nicotine, & caffeine)amphetamines, hallucinogens, "ecstasy", opiates, sedatives, pain pills, sleeping pills or other psychoactive drugs within two weeks of the start of the study OR more than 10 times in the last year. - Has a current dependence on, or addiction to any psychoactive drug (except nicotine or caffeine) including alcohol. - Clinically significant medical or psychiatric illness requiring treatment as determined by screening blood tests, medical history, and physical exam performed or reviewed by the study physician. - Subject has a history of major alcohol related complications within the proceeding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, etc.) - Liver function test ≥ 3 times normal upper limit. - BAC level > 0.05% at the beginning of screening visit (within margin of error of detection). - Has a neurological dysfunction or psychiatric disorder. - Has severe low blood pressure. - Has uncontrolled high blood pressure. - Regular use of any of the drugs on the tolcapone or entacapone contraindications list OR within 2 weeks of drug administration. - Regular use of SSRIs. - Has an allergy or intolerance to tolcapone or entacapone. - Subject has received an investigational drug within 30 days of screening visit. - Subject is considered unsuitable for the study in the opinion of the investigator or study physician for any other reason. MRI Exclusion Criteria: - The subject has metal (metal plates, pins, wires or screws, artificial limb, joint replacement or anything that might have been inserted during an operation) in his/her body. - Subject has a pacemaker, defibrillator, stent, or any metal implants related to heart/blood flow problems. - Subject has worked with metals (ie. metallurgy, metal shaving, welding, soldering, etc). - Subject has been wounded with anything metal (bullet, shrapnel or metal filling). - Has ever gotten a piece of metal in the eye. - Has tattoos done with ink containing metal or permanent eyeliner. - Wears color contact lenses. - Has a hearing problem or hearing aid, cochlear implant or past ear surgery. - Has any irremovable dental bridges, dental plates, metal caps or any other non-removable metal in the mouth. - The subject is claustrophobic. - The subject is pregnant. (women only) - Has a IUD. (women only) - Significantly overweight.

Additional Information

Official title A Randomized, Double-Blind Study of Neural Circuit Responses to COMT Inhibitors
Principal investigator Howard Fields, MD, PhD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by University of California, San Francisco.