Decision Making
Conditions
Brief summary
Numerous psychiatric and neurodegenerative diseases like schizophrenia, dependency on drugs of abuse, depression and Parkinson's disease are related to motivational and cognitive deficits in value-based decision making, which frequently persist even after a successful pharmacological treatment. According to current neurobiologic models, cortical dopamine D1 receptors play a crucial role in taking value-based decisions. In this study, it will be investigated whether value-based decisions in healthy volunteers can be improved by stimulation of D1-receptors. For this purpose, a newly developed dopamine D1-agonist will be used, which selectively increases the activities of frontal D1- and D5-receptors. In this double-blind, randomized, placebo-controlled study, the effects of different single doses of PF-06412562, a not yet licensed D1-agonist, on value-based decision making will be compared with placebo. The use of different dosage strengths will allow to investigate a potential relationship between the extent of activity of the D1-receptor and its influence on behavioral indices. Therefore, four parallel groups will be investigated. Each participant takes in a single dose of either PF-06412562 in different doses or placebo. A screening exam will be carried out 1-3 weeks before the drug intake, and a follow-up examination will be carried out approx. 1 week after the drug intake. At all 3 visits in the study centre, several tests for the investigation of value-based decision making will be carried out.
Interventions
DRUGPF-06412562
double-blind oral intake of single doses of the aforementioned drug or placebo
DRUGPlacebo
double-blind oral intake of single doses of the aforementioned drug or placebo
Sponsors
Pfizer
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Informed Consent as documented by signature on the informed consent form * Physically and psychiatrically healthy men and women * Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days for females and 90 days for males after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children. * Female subjects of non childbearing potential must meet at least one of the following criteria: * Have undergone a documented hysterectomy and/or bilateral oophorectomy; * Have medically confirmed ovarian failure or; * Achieved post menopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the post menopausal state. * All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential. * Aged 18-35 years * Negative pregnancy test (see
Exclusion criteria
) * Normal or corrected-to-normal vision
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of PF-06412562 on a probabilistic reversal learning task (compared to placebo). | 5 hours after drug intake. | This validated computer-based decision-making task tests different aspects of value-based decision making. It will be carried out by each participant immediately after the test in outcome 5. |
| Effect of PF-06412562 on the Pavlovian to instrumental transfer task (compared to placebo). | 5 hours after drug intake. | This validated computer-based decision-making task tests Pavlovian acquisition and transfer. It will be carried out by each participant immediately after the test in outcome 3. |
| Effect of PF-06412562 on an exploration / exploitation task (compared to placebo). | 5 hours after drug intake. | This validated computer-based decision-making task tests different aspects of value-based decision making. It will be carried out by each participant immediately after the test in outcome 4. |
| Change from baseline in a delay discounting task. | 1-3 weeks before (= baseline), 5 hours after, and approx. 1 week after drug intake. | This validated computer-based decision-making test will be filled in by each participant at three time points during the study: 1-3 weeks before, 5 hours after, and approx. 1 week after a single oral intake of 1 out of 3 possible doses of PF-06412562, or matching placebo. |
| Change from baseline in a risk discounting task. | 1-3 weeks before (= baseline), 5 hours after, and approx. 1 week after drug intake. | This validated computer-based decision-making test will be filled in by each participant at three time points during the study: 1-3 weeks before, 5 hours after, and approx. 1 week after a single oral intake of 1 out of 3 possible doses of PF-06412562, or matching placebo. It will be carried out after the test for outcome 1. |
| Effect of PF-06412562 on an effort discounting task (compared to placebo). | 5 hours after drug intake. | This validated computer-based decision-making test will be completed by each participant 5 hours after a single oral intake of 1 out of 3 possible doses of PF-06412562, or matching placebo and after having completed the tests for outcome 1 and 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (safety and tolerability of PF-06412562) | throughout the study and up to 1 week after study drug intake. | continuous assessment of adverse events by non-leading questions, repeated safety laboratory tests, repeated ECGs, repeated control of vital parameters. |
Other
| Measure | Time frame |
|---|---|
| Plasma concentrations of PF-06412562 | blood sampling 4 hours and 8 hours after the study drug intake. |
Countries
Switzerland
Outcome results
None listed