Pathological Gambling
Conditions
Keywords
decision making, impulsivity
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.
Detailed description
Tolcapone increases the effects of dopamine in the brain. Dopamine is a substance that is normally present in the brain. It may increase body movement and may also change a person's ability to process information. Tolcapone stops one's own naturally-released dopamine from being broken down as quickly. The investigators are interested in learning if tolcapone has positive effects on a person's decisions about rewards.
Interventions
DRUGTolcapone
Tolcapone is in the medication class of catechol-O-methyltransferase (COMT) inhibitors
DRUGPlacebo
A placebo is a tablet or capsule that looks like the study medication (in this case, tolcapone) but does not contain any active ingredients
Sponsors
National Center for Responsible Gaming
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
This study is a single-group study in which subjects received both placebo and tolcapone in a randomized, double-blind, counterbalanced, within-subject design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
This behavioral and fMRI study will recruit alcohol drinkers who also participate in gambling activities. Subjects will be selected in an unbiased fashion with respect to gender and ethnicity, as minority representation issues do not interact with any of the hypotheses. To be eligible to participate in the study, the following inclusion criteria must also be met: 1. Subject is a healthy volunteer between 18-50 years of age. 2. Subject is right handed (important for interpreting MRI activity). 3. 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). 4. Subject is able to read and speak English. 5. Subject is a high school graduate. 6. Subject is able and willing to provide written informed consent. 7. Subject is able to understand and follow the instructions of the investigator, and understand all ratings scales. 8. Subject is in good health.
Exclusion criteria
• In order to assess potential contraindications to tolcapone, blood will be tested for routine chemistries including white cell count, red cell count, platelet count, hemoglobin, hematocrit, MCV, MCH, MCHC, RDW, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Additionally, a hepatic screen will assay total protein, albumin, globulin, A/G ratio, bilirubin (total, direct, and indirect), alkaline phosphatase, AST (SGOT), and ALT (SGPT). Elevation of plasma bilirubin, AST (SGOT), ALT (SGPT), or alkaline phosphatase consistent with liver disease will be grounds for subject exclusion. (Note that ongoing monitoring of liver enzymes will not be necessary, as only a single, counterbalanced dose of tolcapone will be administered to each subject.) Subjects will additionally be urine-screened for illicit drug use and screened for alcohol intoxication via breathalyzer. The 7 drug classes detected include cocaine, amphetamine, methamphetamine, benzodiazepines, THC, opiates & oxycodone. These drugs have been chosen due to their possible interaction with tolcapone and possible cognitive and cardiovascular effects. No identifiers will be put on the test cup and it will be read immediately and discarded by the researcher. Similarly, the results of the breathalyzer will be read and then the test will be discarded. No personal identifiers will be associated with the test results. Subjects who test positive for any of these substances, with the exception of THC, will be excluded from further participation in the study. Subjects who have used any psychoactive drugs (except marijuana) within 2 weeks of the start of the study or more than 10 times in the last year will be excluded from participation in the study. 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. Active use of substances other than alcohol, tobacco, or marijuana, use of alcohol on the day of the meeting as assessed by breathalyzer testing, reported marijuana use in the 48 hours preceding a testing visit, and/or a positive pregnancy test, will be grounds for exclusion. 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. Known allergy or intolerance to tolcapone or use of an investigational drug within 30 days of the screening visit will be grounds for exclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between the Impulsive Choice Ratio and Baseline Impulsivity, as Measured With the Barratt Impulsiveness Scale, Non-planning Subscale | 120 minutes after drug ingestion | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | The presented value represents a correlation. The difference in performance on the delay discounting task was calculated as the change in ICR (tolcapone minus placebo). In addition, the difference in BOLD activity throughout the brain was determined (tolcapone minus placebo). |
Participant flow
Recruitment details
Patients were recruited from the community between June 2014 and September 2015.
Participants by arm
| Arm | Count |
|---|---|
| Functional MRI Arm 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
Tolcapone: Tolcapone is in the medication class of catechol-O-methyltransferase (COMT) inhibitors
Placebo: A placebo is a tablet or capsule that looks like the study medication (in this case, tolcapone) but does not contain any active ingredients | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Functional MRI Arm |
|---|---|
| Age, Continuous | 31.5 years STANDARD_DEVIATION 8.9 |
| Barratt Impulsiveness Scale, Non-planning Subscale | 25.6 units on a scale STANDARD_DEVIATION 4.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 17 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 0 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
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.
Time frame: 120 minutes after drug ingestion
Population: The outcome for this study was the correlation between the BIS score, non-planning subscale, and the difference in ICR (tolcapone minus placebo). As such, one Arm/Group is presented below.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Functional MRI Arm (Tolcapone and Placebo) | Correlation Between the Impulsive Choice Ratio and Baseline Impulsivity, as Measured With the Barratt Impulsiveness Scale, Non-planning Subscale | -0.5 Correlation coefficient |
Comparison: The comparison group represents the difference in ICR and the baseline impulsiveness scale, non-planning subscale.p-value: 0.04Fisher transformation
Other Pre-specified
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)
The presented value represents a correlation. The difference in performance on the delay discounting task was calculated as the change in ICR (tolcapone minus placebo). In addition, the difference in BOLD activity throughout the brain was determined (tolcapone minus placebo).
Time frame: 120 minutes after drug ingestion
Population: The outcome for this study was the correlation between the difference in the ICR and the difference in BOLD activity (tolcapone minus placebo). As such, one Arm / Group is presented below.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Functional MRI Arm (Tolcapone and Placebo) | 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) | -0.76 Correlation coefficient |
p-value: <0.05Fisher transformation