A Study of Neural Circuit Responses to Catechol-O-methyl Transferase (COMT) Inhibitors

NCT01158950 | Completed Results

• 2 other identifiers: 2009-12-461W81XWH-10-1-0231
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

In this study, we seek to understand the effects of tolcapone, an FDA-approved COMT inhibitor, 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.

Conditions

Impulsive Behavior

Outcome Measures

Primary Outcomes (1)

• Correlation Between the Impulsive Choice Ratio and Baseline Impulsivity, as Measured With the Barratt Impulsiveness Scale

  The presented value represents a correlation. Subjects completed a delay discounting task while functional MRI images were obtained. In this task, subjects made hypothetical choices between a smaller amount of money available sooner, and a larger amount of money available later. Performance on the delay discounting task, as assessed by the impulsive choice ratio, was determined for both the tolcapone and placebo sessions, and the difference between them (tolcapone minus placebo) was calculated. This difference value was then correlated with baseline scores on the Barratt Impulsiveness Scale.

  120 minutes after drug ingestion

Other Outcomes (1)

• Correlation Between the Difference in ICR (Tolcapone Minus Placebo) and the Difference in Blood Oxygen Level Dependent (BOLD) Signal in the Brain (Tolcapone Minus Placebo)

  120 minutes after drug ingestion

Study Arms (2)

Tolcapone

EXPERIMENTAL

Drug: Tolcapone 200mg (single dose) administered at study visit

Drug: Tolcapone

Placebo

PLACEBO COMPARATOR

Drug: Placebo for tolcapone administered at study visit

Other: Placebo

Interventions

Tolcapone DRUG

Drug: Tolcapone 200mg (single dose) administered at study visit

Also known as: Tasmar

Tolcapone

Placebo OTHER

Placebo (200mg) administered at study visit

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of California, Berkeley: collaborator
• United States Department of Defense: collaborator

Study Sites (2)

University of California, Berkeley

Berkeley, California, 94704, United States

Location

UCSF: Ernest Gallo Clinic and Research Center

Emeryville, California, 94591, United States

Location

Related Publications (1)

• Kayser AS, Allen DC, Navarro-Cebrian A, Mitchell JM, Fields HL. Dopamine, corticostriatal connectivity, and intertemporal choice. J Neurosci. 2012 Jul 4;32(27):9402-9. doi: 10.1523/JNEUROSCI.1180-12.2012.

  PMID: 22764248 RESULT

MeSH Terms

Conditions

Impulsive Behavior

Interventions

Tolcapone

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitrophenols; Phenols; Ketones; Nitro Compounds

Limitations and Caveats

Funding constrained the number of participants. Describing the thousands of statistical tests in neuroimaging studies is not possible within this reduced format. Please see the open access pdf of Kayser et al, JNeurocience 2012.

Results Point of Contact

• Title: Dr. Jennifer Mitchell
• Organization: University of California, San Francisco

jennifer.mitchell@ucsf.edu

510-985-3522

Study Officials

• Howard Fields, MD, PhD

  UCSF: Ernest Gallo Clinic and Research Center

  PRINCIPAL INVESTIGATOR

• Jennifer Mitchell, PhD

  UCSF: Ernest Gallo Clinic and Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2010
• First Posted: July 8, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: November 20, 2020
• Results First Posted: November 20, 2020

Record last verified: 2020-11

Locations

US (2)