Studying the Role of Brain Molecules for Decision Making

NCT04384562 | Completed DMC

• 1 other identifier: 2020-00044-BEH
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Decision Making; Healthy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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 in the main experimental session before drug/placebo administration and through study completion lasting about 1 hour.

Other Outcomes (1)

• Computational parameters estimated from experimental data

  All participants perform decision-making tasks after drug/placebo administration in the main experimental session lasting about 1 hour.

Study Arms (4)

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.

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.

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.

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.

Drug: Placebo pill; Drug: Placebo gum

Interventions

Methylphenidate DRUG

A 20 mg methylphenidate (Ritalin®) is administered only once for the dopamine reuptake inhibitor group.

Also known as: Ritalin®

Dopamine reuptake inhibitor

Reboxetine DRUG

A 4 mg reboxetine (Edronax®) is administered only once for the noradrenaline reuptake inhibitor group.

Also known as: Edronax®

Noradrenaline reuptake inhibitor

Nicotine gum DRUG

A 2 mg nicotine (Nicorette®) gum is administered only once for the cholinergic receptor agonist group.

Also known as: Nicorette®

Cholinergic receptor agonist

Placebo pill DRUG

A placebo pill is administered only once.

Cholinergic receptor agonist; Placebo

Placebo gum DRUG

A placebo gum is administered only once.

Dopamine reuptake inhibitor; Noradrenaline reuptake inhibitor; Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

University of Zurich

Zurich, 8006, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 37639601 DERIVED

MeSH Terms

Interventions

Methylphenidate; Reboxetine; Nicotine Chewing Gum

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Chewing Gum; Plant Gums; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Tobacco Use Cessation Devices; Therapeutics; Candy; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Philippe Tobler, PhD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: All participants will receive the same instructions, and neither they nor the experimenters are informed which drug is used. Participants must take the drug in front of the investigator, to ensure correct intake and compliance.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 10, 2020
• First Posted: May 12, 2020
• Study Start: December 17, 2020
• Primary Completion: December 13, 2021
• Study Completion: December 13, 2021
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

CH (1)