Studying the Role of Brain Molecules for Decision Making

May 7, 2024 updated by: University of Zurich
The aim of the present project is to elucidate the neuropharmacological mechanisms underlying value (choice preference) and attention (choice randomness) processing in humans. More specifically, the investigators test whether dopaminergic, noradrenergic and cholinergic interventions affect neural and behavioral processing of valuation and attention during decision-making. The investigators do this by up-regulating dopaminergic, noradrenergic or cholinergic neurotransmission pharmacologically through administration of methylphenidate, reboxetine, or nicotine. We test the hypothesis that methylphenidate, reboxetine, or nicotine reduce choice randomness and that this effect is underpinned by an effect on attention and/or value processing.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

To simultaneously assess and dissociate choice preference and randomness in stable environments, the investigators plan to use two tasks: (1) a variant of the RISKGARP task, a well-established risky decision-making task and (2) a modified Becker-DeGroot-Marshak task that measures choice preference and the width of preference representations with the range of willingness to pay procedure (range-WTP). Note that wider representations should result in more choice randomness. The investigators will assess choice randomness also by repeating the same decision questions several times within each task and by relating the preferences measured by the RISKGARP task to those measured by the range-BDM task by using the same options in both tasks. To assess the impact of changing environments and learning on choice preference and randomness, participants will perform two established exploration/exploitation tasks. One (3) is a foraging task that has been combined with different pharmacological manipulations and the other (4) is a variant of the four-armed bandit task, which allows distinguishing value- or information-based exploration from random choice. Blood and saliva samples may be taken. Blood samples may be used to determine levels of the administrated substances and to assess genetic variation. Saliva samples may be used to determine cortisol and testosterone levels.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
160

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Switzerland
      • Zurich, Switzerland, 8006
        • University of Zurich

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 31 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Physically and psychiatrically healthy (as defined by exclusion criteria) men and women aged 18-35 years
  • Ability and willingness to participate in the study
  • Willingness to not eat or drink any food/beverage containing caffeine or alcohol 12 hours prior to the administration of study medication (asked in screening session)
  • Willingness to not eat or drink grapefruit or grapefruit related citrus fruits (e.g., Seville oranges, pomelos) from 7 days prior to the administration of study medication (asked in screening session)
  • Good command of English language (be able to understand the task instructions and in the unlikely case of adverse effects inform the examiner)
  • Signed informed consent

Exclusion Criteria:

  • Serious past brain disease or injury
  • Frequent headaches (of any sort, > 1/week) or migraine (irrespective of frequency)
  • History of epileptic seizures
  • Any neurological disorder
  • Surgery to head or heart (MRI safety, potential metal pieces)
  • Pacemaker, hearing aid or neurostimulator (MRI safety, metal pieces)
  • Known cardiac or cardiovascular disease or anomaly
  • Family history of sudden death due to cardiac arrhythmia
  • High or low blood pressure, history of heart attack, infrequent heartbeat
  • Respiratory problems (including difficulty with breathing through the nose)
  • Glaucoma (present or past)
  • Insufficiency of kidney or liver, acute liver disease
  • Any psychiatric disorder (especially depression, mania, schizophrenia, addiction panic and suicidality)
  • Severe vocal or motor tics (methylphenidate, data quality)
  • Severe psychosomatic disorder (somatic complaints without clear medical cause, has a mental component)
  • Potential metal parts in body (MRI safety; metal splinters, gun wounds, shrapnel or surgical clips)
  • Pregnancy, nursing, or currently planned pregnancy
  • Allergy to drugs, particularly methylphenidate, reboxetine or nicotine
  • Severe intolerance to lactose including strong diarrhea after only a few mg (weak lactose intolerance is no exclusion criterion as medication only contains a very small dose (around 4 mg) of lactose)
  • Oversensitivity to hot pepper sauce (e.g., tabasco)
  • Currently taking any medication or recently participated in other clinical trials that might interfere with Methylphenidate and Reboxetine, especially MAO-Inhibitors (e.g. Aurorix (Moclobemid) and Azilect (Rasagilin), antipsychotics, antibiotics, and medication for heart diseases
  • Currently taking any further medication (besides birth control) or natural products (infrequent intake of natural products and/or food supplements need to be mentioned to the examiner)
  • Drug abuse (exclude people with a positive test)
  • Serious acute or chronic disease that could interfere with participation in the experiments
  • Inability to lie still in the scanner (e.g. due to itching, sneezing, coughing, claustrophobia)
  • Inability to understand the instructions
  • Participants with BMI < 18
  • Clinically relevant score in STAI T (anxiety), measured during screening on a separate day
  • ECG demonstrating QTcF >450 msec or a QRS interval >120 msec at screening. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF/QRS values should be used to determine participant eligibility, measured during screening on a separate day
  • Participants who eat or drink grapefruit or grapefruit related citrus fruits (e.g., Seville oranges, pomelos) or drinks from 7 days prior to the administration of study medication.
  • Participants who eat or drink any food/beverage containing caffeine or alcohol 12 hours before the study
  • Current smokers/tobacco consumers (exclude people whose cotinine level is higher than 50ng/ml with a urine test)
  • Phenylketonuria
  • Dental or jaw condition prohibiting gum chewing
  • Pheochromocytoma
  • Thyroid disorders
  • Diabetes
  • Type of angina where chest pain occurs at rest
  • Unpredictable severe constricting chest pain
  • Prickling or tingling of fingers and toes
  • Buerger's Disease
  • Throat irritation
  • Peptic ulcers
  • Esophagitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dopamine reuptake inhibitor
Participants in the dopamine reuptake inhibitor group will be asked to take one pill containing 20 mg methylphenidate 1.5 hours before the experimental session. One hour later (30 minutes before testing begins), participants will be asked to chew a placebo gum.
Drug: Methylphenidate
A 20 mg methylphenidate (Ritalin®) is administered only once for the dopamine reuptake inhibitor group.
Other Names:
  • Ritalin®
Drug: Placebo gum
A placebo gum is administered only once.
Experimental: Noradrenaline reuptake inhibitor
Participants in the noradrenaline reuptake inhibitor group will be asked to take one pill containing 4 mg reboxetine 1.5 hours before the experimental session. One hour later (30 minutes before testing begins), participants will be asked to chew a placebo gum.
Drug: Placebo gum
A placebo gum is administered only once.
Drug: Reboxetine
A 4 mg reboxetine (Edronax®) is administered only once for the noradrenaline reuptake inhibitor group.
Other Names:
  • Edronax®
Experimental: Cholinergic receptor agonist
Participants in the cholinergic receptor agonist group will be asked to take a placebo pill 1.5 hours before the experimental session. One hour later (30 minutes before testing begins), participants will be asked to chew a gum with 2 mg of nicotine.
Drug: Nicotine gum
A 2 mg nicotine (Nicorette®) gum is administered only once for the cholinergic receptor agonist group.
Other Names:
  • Nicorette®
Drug: Placebo pill
A placebo pill is administered only once.
Placebo Comparator: Placebo
Participants in the placebo group will be asked to take a placebo pill 1.5 hours before the experimental session. One hour later (30 minutes before testing begins), participants will be asked to chew a placebo gum.
Drug: Placebo gum
A placebo gum is administered only once.
Drug: Placebo pill
A placebo pill is administered only once.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Choice data
Time Frame: All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.
Choice data made by participants are measured from the experimental tasks. More specifically, the investigators calculate choice preferences, such as the percentage of trials in which participants chose options with probabilistic outcomes in the RISKGARP task and the bids they made in the Range-WTP task, the percentage of exploitative/explorative choices in the four-armed bandit task, and the leaving time in the foraging task. Moreover, the investigators determine choice sub-optimality, such as the number of choices violating transitivity in the RISKGARP task, the inconsistency of bids in repeated trials in the Range-WTP task, the percentage of selecting the worst option in the four-armed bandit task, and the difference between optimal leaving time and actual leaving time in the foraging task.
All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.
Response time data
Time Frame: All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.
Response times are measured from experimental tasks. The investigators calculate how long participants take to make decisions in each trial.
All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The size of pupil dilation
Time Frame: Pupil size is measured in the main experimental session before drug/placebo administration and through study completion lasting about 1 hour.
Pupil size is measured using eye-tracker while participants perform the experimental tasks. Baseline pupil size is also measured before the drug/placebo administration.
Pupil size is measured in the main experimental session before drug/placebo administration and through study completion lasting about 1 hour.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Computational parameters estimated from experimental data
Time Frame: All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.
Computational parameters are estimated from the data of participants during the decision-making tasks. Specifically, mathematical models will be applied to above-mentioned choice data and/or response time data. The estimated parameters reflect choice preference and stochasticity and are complementary to the descriptive measurements mentioned above. For example, utility functions will be estimated and the choice preferences are described by the concavititvity of utility functions.
All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Zurich

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Philippe Tobler, PhD, University of Zurich

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 17, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 13, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 13, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 10, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 12, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020-00044-BEH

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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