HealthyNCT04371146
The Role of Dopaminergic and Noradrenergic Neurotransmission in Value- and Salience-based Decision-Making
A study testing Methylphenidate and Reboxetine in people with Healthy, run by University of Zurich at 1 site in Switzerland.
Trial summary
Approach versus avoidance decisions are at the centre of adaptive behaviour and survival. These decisions are thought to be guided by the value of the choice options, which are a function of the magnitude of predicted rewards and punishments. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Methylphenidate and Reboxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteSwitzerland
- Study dates
- 3 Jul 2019to 13 Feb 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Physically and psychiatrically healthy men and women aged ≥ 18- ≤ 35 years
- Ability and willingness to participate in the study
- Signed informed consent
Who cannot join
- Serious past brain disease or injury (data quality)
- Frequent headaches (of any sort, > 1/week) or migraine (irrespective of frequency)
- History of epileptic seizures
- Any neurological disorder
- Surgery to head or heart (safety, potential metal pieces)
- Pacemaker, hearing aid or neurostimulator (safety, metal pieces)
Show all 26Show fewer
- 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 in history)
- Insufficiency of kidney or liver, acute liver disease
- Any psychiatric disorder (especially depression, mania, schizophrenia, addiction and suicidality)
- Severe vocal or motor tics (methylphenidate, data quality)
- Severe psychosomatic disorder (somatic complaints without clear medical cause, has a mental component)
- Pregnancy, nursing, or currently planned pregnancy
- Current allergy in general or allergy to methylphenidate or reboxetine
- Severe intolerance to lactose including strong diarrhea after only a few mg (weak lactose intolerance is no exclusion criterion as medication only contains slightest dosage (around 4mg) of lactose)
- Currently taking any medication that might interfere with Methylphenidate and Reboxetine, especially MAO-Inhibitors (e.g. Aurorix (Moclobemid) und 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 (current or past abuse; in case of single use please inform the examiner)
- Serious acute or chronic disease that could interfere with participation in the experiments
- Inability to understand the instructions or insufficient comprehension of German language
- Participants having their weight outside of the range of ≥ 60 kg - ≤ 80 kg
- Clinically relevant score in STAI T (anxiety), measured during prescreening on a separate day
- Long QT syndrome or other arrhythmias, measured during prescreening on a separate day
Trial locations and contacts
1 site in 1 country.
About this study
Approach versus avoidance decisions are at the centre of adaptive behaviour and survival. These decisions are thought to be guided by the value of the choice options, which are a function of the magnitude of predicted rewards and punishments. Moreover, the allocation of attention to choice options is thought to be driven by salience, i.e. the overall importance of the predicted outcomes. While salience increases with the magnitude of both predicted rewards and predicted punishments, value increases with reward but decreases with punishment. In previous research, value and salience have often remained confounded during value-based decision making. Rodent research suggests that value is associated with dopamine and salience with norepinephrine. The present study aims at disentangling value from salience processing during decision-making tasks in healthy subjects by administering dopamine or noradrenaline reuptake inhibitors. This is done by using a single dose challenge in a randomized placebo-controlled between subject's design, administering either methylphenidate (35 mg), reboxetine (8 mg), or placebo to healthy young participants before they perform tasks tapping into various aspects of value and salience.
- Conditions
- Healthy
- Being tested
- Methylphenidate, Reboxetine, Placebos
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylphenidateDrug
Also called Ritalin®
35 mg methylphenidate (Ritalin®) is administered once using a randomized placebo-controlled between subject's design
ReboxetineDrug
Also called Edronax®
8 mg Reboxetine (Edronax®) is administered once using a randomized placebo-controlled between subject's design
PlacebosDrug
Also called Placebo Pill
A placebo pill is administered once using a randomized placebo-controlled between subject's design
| Study group | Role | What they receive |
|---|---|---|
| Dopamine reuptake inhibitor | Experimental | Participants in the dopamine reuptake inhibitor group will be asked to take one pill containing 35 mg methylphenidate 1.5 hours before performing the tasks. Receives: Drug: Methylphenidate |
| Noradrenaline reuptake inhibitor | Experimental | Participants in the noradrenaline reuptake inhibitor group will be asked to take one pill containing 8 mg reboxetine 1.5 hours before performing the tasks. Receives: Drug: Reboxetine |
| Placebo | Placebo comparator | Participants in the placebo group will be asked to take a placebo pill 1.5 hours before performing the tasks. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response time data
The investigators record responses and specifically reaction times during 5 different decision-making tasks.
In a value vs salience task, value and salience processing is disentangled during value-based decision-making. Participants either accept or reject compound stimuli that were before associated with monetary outcomes.
In a face in the crowd task, participants detect a target face (angry vs happy) in a crowd of opposite face type.
During a task on risk and ambiguity decision-making, participants have to decide between safe and lottery options associated with either monetary risk or ambiguity.
In an adaptive risk-taking task, participants have to choose between two risky monetary options.
In an effort task, participants decide whether they are willing to exert physical effort for monetary reward.
Response times are measured in milliseconds from the tasks. The investigators calculate how long participants take to make decisions in each trial.
Measured: These tasks take place 1,5 hours after the drug was administered
Choice data
As a dependent variable the investigators record responses and specifically choices made during the above-mentioned different decision-making tasks. The investigators evaluate what kind of answers were made during each trial of the decision-making tasks, in respect to correctness or preference (percentage).
Measured: These tasks take place 1,5 hours after the drug was administered
Secondary outcomes (2)
Computational modelling applied to choice data
Computational parameters are mathematically estimated from the data of participants during the above-mentioned decision-making tasks. Specifically, mathematical models will be applied to choice data (percentage).
Measured: These tasks take place 1,5 hours after the drug was administered
Computational modelling applied to response time data
Computational parameters are mathematically estimated from the data of participants during the above-mentioned decision-making tasks. Specifically, mathematical models will be applied to response time data (milliseconds).
Measured: These tasks take place 1,5 hours after the drug was administered
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2020
- Study start3 Jul 2019
- Primary completion13 Feb 2020
- Study completion13 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The investigators implement a randomized, double-blind, placebo-controlled between-subjects design, using one factor (pharmacological intervention) with three levels (reboxetine, methylphenidate and placebo).
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippe Tobler, PhD, Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04371146
- Sponsor's protocol ID
- Value-Salience-2017-0444
- Status last verified
- Apr 2020
- First submitted
- 26 Apr 2020
- Last updated
- 1 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Dopaminergic and Noradrenergic Neurotransmission in Value- and Salience-based Decision-Making
- ClinicalTrials.gov ID
- NCT04371146
- Acronym / sponsor ID
- Value-Salience-2017-0444
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 3 Jul 2019 (actual)
- Primary completion
- 13 Feb 2020 (actual)
- Study completion
- 13 Feb 2020 (actual)
- First posted
- 1 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approach versus avoidance decisions are at the centre of adaptive behaviour and survival. These decisions are thought to be guided by the value of the choice options, which are a function of the magnitude of predicted rewards and punishments. Moreover, the allocation of attention to choice options is thought to be driven by salience, i.e. the overall importance of the predicted outcomes. While salience increases with the magnitude of both predicted rewards and predicted punishments, value increases with reward but decreases with punishment. In previous research, value and salience have often remained confounded during value-based decision making. Rodent research suggests that value is associated with dopamine and salience with norepinephrine. The present study aims at disentangling value from salience processing during decision-making tasks in healthy subjects by administering dopamine or noradrenaline reuptake inhibitors. This is done by using a single dose challenge in a randomized placebo-controlled between subject's design, administering either methylphenidate (35 mg), reboxetine (8 mg), or placebo to healthy young participants before they perform tasks tapping into various aspects of value and salience.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- The investigators implement a randomized, double-blind, placebo-controlled between-subjects design, using one factor (pharmacological intervention) with three levels (reboxetine, methylphenidate and placebo).
| Arm | Type | Receives |
|---|---|---|
| Dopamine reuptake inhibitor | Experimental | Drug: MethylphenidateParticipants in the dopamine reuptake inhibitor group will be asked to take one pill containing 35 mg methylphenidate 1.5 hours before performing the tasks. |
| Noradrenaline reuptake inhibitor | Experimental | Drug: ReboxetineParticipants in the noradrenaline reuptake inhibitor group will be asked to take one pill containing 8 mg reboxetine 1.5 hours before performing the tasks. |
| Placebo | Placebo comparator | Drug: PlacebosParticipants in the placebo group will be asked to take a placebo pill 1.5 hours before performing the tasks. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Physically and psychiatrically healthy men and women aged ≥ 18- ≤ 35 years
- Ability and willingness to participate in the study
- Signed informed consent
Key exclusion criteria (26 listed)
- Serious past brain disease or injury (data quality)
- Frequent headaches (of any sort, > 1/week) or migraine (irrespective of frequency)
- History of epileptic seizures
- Any neurological disorder
- Surgery to head or heart (safety, potential metal pieces)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylphenidateAlso: Ritalin®35 mg methylphenidate (Ritalin®) is administered once using a randomized placebo-controlled between subject's design | Drug | Dopamine reuptake inhibitor |
| ReboxetineAlso: Edronax®8 mg Reboxetine (Edronax®) is administered once using a randomized placebo-controlled between subject's design | Drug | Noradrenaline reuptake inhibitor |
| PlacebosAlso: Placebo PillA placebo pill is administered once using a randomized placebo-controlled between subject's design | Drug | Placebo |
Primary outcome
Response time data
Time frame: These tasks take place 1,5 hours after the drug was administered
The investigators record responses and specifically reaction times during 5 different decision-making tasks. In a value vs salience task, value and salience processing is disentangled during value-based decision-making. Participants either accept or reject compound stimuli that were before associated with monetary outcomes. In a face in the crowd task, participants detect a target face (angry vs happy) in a crowd of opposite face type. During a task on risk and ambiguity decision-making, participants have to decide between safe and lottery options associated with either monetary risk or ambiguity. In an adaptive risk-taking task, participants have to choose between two risky monetary options. In an effort task, participants decide whether they are willing to exert physical effort for monetary reward. Response times are measured in milliseconds from the tasks. The investigators calculate how long participants take to make decisions in each trial.
Choice data
Time frame: These tasks take place 1,5 hours after the drug was administered
As a dependent variable the investigators record responses and specifically choices made during the above-mentioned different decision-making tasks. The investigators evaluate what kind of answers were made during each trial of the decision-making tasks, in respect to correctness or preference (percentage).
2 secondary outcomes
Computational modelling applied to choice data
Time frame: These tasks take place 1,5 hours after the drug was administered
Computational modelling applied to response time data
Time frame: These tasks take place 1,5 hours after the drug was administered
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe Tobler, PhD principal investigator
University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methylphenidate and Reboxetine in people with Healthy, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response time data (time frame: These tasks take place 1,5 hours after the drug was administered). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2020.