Dopaminergic Modulation of Frontostriatal Function With a Dopamine Agonist and COMT Inhibitor

In this study, the investigators are looking at how people make decisions about reward-related items, both monetary and food related after taking either the dopamine agonist bromocriptine or the COMT inhibitor tolcapone, in healthy control subjects. Subjects will fill self-report questionnaires and undergo an MRI scan.

Study Overview

• Status: Withdrawn
• Conditions: Addiction
• Intervention / Treatment: Drug: Tolcapone; Drug: Placebo; Drug: Bromocriptine

Detailed Description

The investigators aim to understand how the brain's dopamine system impacts monetary and food-related decision making. The investigators aim to use tolcapone and bromocriptine due to the temporary change in the levels of dopamine in the brain. The investigators also aim to determine if genetics, personality traits, or a family history of alcoholism change how these drugs affect decision making.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94704
      • University of California, Berkeley
    • San Francisco, California, United States, 94158
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental: Tolcapone; Drug: Tolcapone 200mg (single dose) administered at study visit	Drug: Tolcapone; Tolcapone 200mg (single dose) administered at study visit; Other Names: Tasmar
PLACEBO_COMPARATOR: Comparator: Placebo; Drug: Placebo for tolcapone administered at study visit	Drug: Placebo; Placebo (200mg) administered at study visit
EXPERIMENTAL: Experimental: Bromocriptine; Drug: Bromocriptine 1.25mg (single dose) administered at study visit	Drug: Bromocriptine; Drug: Bromocriptine 1.25 mg (single dose) administered at study visit; Other Names: Parlodel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure Effects of Placebo,Tolcapone, Bromocriptine on Reaction Time	Participants will play the Dictator Game. Behavioral responses to the game during each arm (placebo, tolcapone, and bromocriptine) will be measured by subject reaction time .	3 weeks
Measure Effects of Placebo,Tolcapone, Bromocriptine on Accuracy	Participants will play the Dictator Game. Behavioral responses to the game during each arm (placebo, tolcapone, and bromocriptine) will be measured by subject accuracy (correct or incorrect responses).	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure Observed Changes in Resting State Neural Activity	Resting-state data will be processed off-line using neuroimaging analysis software according to standard procedures for image slice-timing correction, realignment, normalization and smoothing. Changes in regional brain activity will be measured during the placebo, tolcapone and bromocriptine conditions.	3 weeks
Measure Observed Changes in Task Dependent Neural Activity	Task dependent fMRI data will be processed off-line using neuroimaging analysis software according to standard procedures for image slice-timing correction, realignment, normalization and smoothing. Changes in task dependent brain activity will be measured during the placebo, tolcapone and bromocriptine conditions.	3 weeks

Collaborators and Investigators

• Sponsor: University of California, Berkeley
• Collaborators: University of California, San Francisco
• Investigators: Principal Investigator: Andrew Kayser, MD,PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2013
• Primary Completion (ANTICIPATED): January 31, 2018
• Study Completion (ANTICIPATED): January 31, 2018

Study Registration Dates

• First Submitted: September 28, 2016
• First Submitted That Met QC Criteria: October 10, 2016
• First Posted (ESTIMATE): October 11, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 12, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Compulsive Behavior; Impulsive Behavior; Behavior, Addictive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Dopamine Agonists; Dopamine Agents; Hormone Antagonists; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Tolcapone; Bromocriptine
• Other Study ID Numbers: 2011-11-3748

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No