Dopamine Responsivity in Gamblers

NCT02772978 | Completed Results

• 1 other identifier: 10-03082 UCSF
• Study Type: interventional
• Target: 19
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study deals with how people decide between rewards of different value. The investigators want to understand how the brain's dopamine system impacts this kind of decision making. The investigators will use a medication, tolcapone, which can temporarily affect the dopamine system.

Conditions

Pathological Gambling

Keywords

decision making; impulsivity

Outcome Measures

Primary Outcomes (1)

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

  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 scores on the Barratt Impulsiveness Scale, non-planning subscale.

  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 arm

ACTIVE COMPARATOR

This cognitive science study consists of a single "arm" in which all subjects receive both tolcapone and placebo in randomized, double-blind, counterbalanced, crossover fashion

Drug: Tolcapone

placebo arm

PLACEBO COMPARATOR

This cognitive science study consists of a single "arm" in which all subjects receive both tolcapone and placebo in randomized, double-blind, counterbalanced, crossover fashion

Drug: Placebo

Interventions

Tolcapone DRUG

Tolcapone is in the medication class of catechol-O-methyltransferase (COMT) inhibitors

Also known as: Tasmar

tolcapone arm

Placebo DRUG

A placebo is a tablet or capsule that looks like the study medication (in this case, tolcapone) but does not contain any active ingredients

Also known as: Sugar pill

placebo arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is a healthy volunteer between 18-50 years of age.
• Subject is right handed (important for interpreting MRI activity).
• If female, subject is non-lactating, not pregnant and using a reliable contraception method (i.e. abstinence, intrauterine device, 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 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:

• Subjects will also be excluded if they regularly use medications that affect dopamine levels, or will have used these medications within two weeks of tolcapone administration (such as tolcapone, entacapone, or any of the following: levodopa/carbidopa, amantadine, bromocriptine, pergolide, pramipexole, ropinirole, selegeline, isocarboxazid, phenelzine, tranylcypromine, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, fluphenazine, haloperidol, perphenazine, pimozide, thiothixene, trifluoperazine, loxapine, molindone, chlorpromazine, mesoridazine, thioridazine, dextroamphetamine, dexmethylphenidate, dextroamphetamine, or methylphenidate).
• A licensed health care provider will also conduct a brief physical exam. This exam will search for signs of medical illness, including jaundice or abdominal distension associated with liver disease, that would exclude subjects from participating in the study. Subjects with clinically significant medical or psychiatric illnesses requiring treatment as determined by screening blood tests, medical history, and/or physical exam will not be eligible to participate in the study.
• Female subjects will also be screened for pregnancy, as the effects of COMT inhibitors during pregnancy are not adequately known and these compounds can appear in breast milk. (Pregnancy is also a contraindication to MRI scanning). Since subjects may not know they are pregnant, all female subjects recruited to participate in the study will be required to have a urine pregnancy test prior to each session of the study. These requirements will not apply to any female subjects who are post-menopausal.
• For subjects participating in the fMRI, we will administer an extensive questionnaire listing contraindications to MRI scanning. Because the MRI scanner attracts certain metals, subjects who may have metallic objects in their bodies will be excluded. As an additional measure of protection, we will use a hand-held metal detector to screen subjects before entering the scanner. Subjects who experience claustrophobia will also be excluded from participating in the MRI scan.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Center for Responsible Gaming: collaborator

Related Publications (2)

• 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 BACKGROUND

• Kayser AS, Vega T, Weinstein D, Peters J, Mitchell JM. Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers. Neuroimage Clin. 2016 Dec 20;13:339-348. doi: 10.1016/j.nicl.2016.12.022. eCollection 2017.

  PMID: 28066708 RESULT

MeSH Terms

Conditions

Gambling; Impulsive Behavior

Interventions

Tolcapone; Sugars

Condition Hierarchy (Ancestors)

Risk-Taking; Behavior; Disruptive, Impulse Control, and Conduct Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Funding constrained the # of participants \<= 20. Please see the open access journal article (Kayser et al, Neuroimage Clinical, 2016) for full details related to procedures, results, and conclusions for this study.

Results Point of Contact

• Title: Andrew Kayser, MD PhD
• Organization: University of California at San Francisco

Andrew.Kayser@ucsf.edu

415-502-7332

Study Officials

• Andrew Kayser, MD, PhD

  University of California at San Francisco

  PRINCIPAL INVESTIGATOR

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, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a single-group study in which subjects received both placebo and tolcapone in a randomized, double-blind, counterbalanced, within-subject design.

Study Record Dates

• First Submitted: May 12, 2016
• First Posted: May 16, 2016
• Study Start: August 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: February 16, 2021
• Results First Posted: February 16, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share