Decision MakingNCT04384562
Studying the Role of Brain Molecules for Decision Making
A study testing Methylphenidate, Reboxetine and Nicotine gum in people with Decision Making and Healthy, run by University of Zurich at 1 site in Switzerland.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Decision Making, Healthy
- What is being tested?
- Methylphenidate, Reboxetine and Nicotine gum
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteSwitzerland
- Study dates
- 17 Dec 2020to 13 Dec 2021
- 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 (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
Who cannot join
- 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)
Show all 44Show 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 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Decision Making, Healthy
- Being tested
- Methylphenidate, Reboxetine, Nicotine gum, Placebo pill, Placebo gum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylphenidateDrug
Also called Ritalin®
A 20 mg methylphenidate (Ritalin®) is administered only once for the dopamine reuptake inhibitor group.
ReboxetineDrug
Also called Edronax®
A 4 mg reboxetine (Edronax®) is administered only once for the noradrenaline reuptake inhibitor group.
Nicotine gumDrug
Also called Nicorette®
A 2 mg nicotine (Nicorette®) gum is administered only once for the cholinergic receptor agonist group.
Placebo pillDrug
A placebo pill is administered only once.
Placebo gumDrug
A placebo gum is administered only once.
| 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 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. Receives: Drug: Methylphenidate; Drug: Placebo gum |
| Noradrenaline reuptake inhibitor | Experimental | 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. Receives: Drug: Reboxetine; Drug: Placebo gum |
| Cholinergic receptor agonist | Experimental | 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. Receives: Drug: Nicotine gum; Drug: Placebo pill |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo pill; Drug: Placebo gum |
What is being measured
The primary outcome is the main question the study is designed to answer.
Choice data
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.
Measured: All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.
Response time data
Response times are measured from experimental tasks. The investigators calculate how long participants take to make decisions in each trial.
Measured: All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.
Secondary outcomes (1)
The size of pupil dilation
Pupil size is measured using eye-tracker while participants perform the experimental tasks. Baseline pupil size is also measured before the drug/placebo administration.
Measured: Pupil size is measured in the main experimental session before drug/placebo administration and through study completion lasting about 1 hour.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start17 Dec 2020
- Primary completion13 Dec 2021
- Study completion13 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Decision MakingStudies 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
- This is a double-blind, randomized, placebo-controlled, between-participant study. In this experiment. Participants will receive a preferential dopamine reuptake inhibitor, a selective noradrenaline reuptake inhibitor, a natural nicotinic acetylcholine receptor agonist, or placebo under double-blind conditions.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 160 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
- NCT04384562
- Sponsor's protocol ID
- 2020-00044-BEH
- Status last verified
- May 2024
- First submitted
- 10 Apr 2020
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Doren N, Chung HK, Grueschow M, Quednow BB, Hayward-Konnecke H, Jetter A, Tobler PN. Acetylcholine and noradrenaline enhance foraging optimality in humans. Proc Natl Acad Sci U S A. 2023 Sep 5;120(36):e2305596120. doi: 10.1073/pnas.2305596120. Epub 2023 Aug 28.
PubMed 37639601
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studying the Role of Brain Molecules for Decision Making
- ClinicalTrials.gov ID
- NCT04384562
- Acronym / sponsor ID
- 2020-00044-BEH
- Conditions
- Decision Making, Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 17 Dec 2020 (actual)
- Primary completion
- 13 Dec 2021 (actual)
- Study completion
- 13 Dec 2021 (actual)
- First posted
- 12 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.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- This is a double-blind, randomized, placebo-controlled, between-participant study. In this experiment. Participants will receive a preferential dopamine reuptake inhibitor, a selective noradrenaline reuptake inhibitor, a natural nicotinic acetylcholine receptor agonist, or placebo under double-blind conditions.
| Arm | Type | Receives |
|---|---|---|
| Dopamine reuptake inhibitor | Experimental | Drug: Methylphenidate, Drug: Placebo gumParticipants 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. |
| Noradrenaline reuptake inhibitor | Experimental | Drug: Reboxetine, Drug: Placebo gumParticipants 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. |
| Cholinergic receptor agonist | Experimental | Drug: Nicotine gum, Drug: Placebo pillParticipants 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. |
| Placebo | Placebo comparator | Drug: Placebo pill, Drug: Placebo gumParticipants 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (44 listed)
- 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)
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®A 20 mg methylphenidate (Ritalin®) is administered only once for the dopamine reuptake inhibitor group. | Drug | Dopamine reuptake inhibitor |
| ReboxetineAlso: Edronax®A 4 mg reboxetine (Edronax®) is administered only once for the noradrenaline reuptake inhibitor group. | Drug | Noradrenaline reuptake inhibitor |
| Nicotine gumAlso: Nicorette®A 2 mg nicotine (Nicorette®) gum is administered only once for the cholinergic receptor agonist group. | Drug | Cholinergic receptor agonist |
| Placebo pillA placebo pill is administered only once. | Drug | Cholinergic receptor agonist, Placebo |
| Placebo gumA placebo gum is administered only once. | Drug | Dopamine reuptake inhibitor, Noradrenaline reuptake inhibitor, Placebo |
Primary outcome
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.
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.
1 secondary outcome
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.
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 8 May 2024.
- Derived from this study: PubMed 37639601Doren N, Chung HK, Grueschow M, Quednow BB, Hayward-Konnecke H, Jetter A, Tobler PN. Acetylcholine and noradrenaline enhance foraging optimality in humans. Proc Natl Acad Sci U S A. 2023 Sep 5;120(36):e2305596120. doi: 10.1073/pnas.2305596120. Epub 2023 Aug 28.
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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, Reboxetine and Nicotine gum in people with Decision Making and 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 6 inclusion and 44 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 8 May 2024. 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?
Choice data (time frame: All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.). 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?
On the ClinicalTrials.gov record for NCT04384562, which also lists 1 linked publication.
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 8 May 2024.