The Role of the Brain in Mental and Physical Fatigue

NCT05880342 | Recruiting Phase 3

• 1 other identifier: G095422N
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine the role of brain neurotransmission in the onset of fatigue, identify the brain areas involved, and determine how brain activity and neuromuscular efficiency changes during onset of fatigue. Three different experimental studies (physical fatigue, mental fatigue and combined) will be performed with a randomized, single-blinded, placebo controlled, counter-balanced, cross-over design. The objectives of the projects are as follows:

• To experimentally assess the role of a dopamine, and a noradrenalin reuptake inhibitor in the onset of exercise-induced fatigue
• To identify changes in brain activation associated with altered PF and fatigue perception
• To experimentally assess the effect of a NA or DA reuptake inhibitor on MF, brain activation and the sources of changes in brain activation
• To experimentally assess the role of brain neurotransmitters (DA, NA) in the interaction between mental and PF from a neurophysiological perspective. Participants will be healthy young adults. In each study, they will start with a familiarization trial followed by two experimental trials and one control trial with a randomized treatment order. At each visit, different drugs will be administered to elicit different neurotransmitter response. The trials will be performed at the MFYS exercise lab (BLITS, VUB campus Etterbeek, Boulevard General Jaques 271, 1050 Elsene (Brussels)). Depending on the type of study they are participating in, participants will perform three distinct tasks:
• In the first experimental study participants will perform a 60-min Stroop Task to elicit mental fatigue.
• In the second experimental study participants will perform a knee-extension exercise until exhaustion to elicit physical fatigue.
• In third experimental study participants will first preform a mental fatiguing task (Stroop taks) followed by physical fatigue task (knee extension). While participants will perform above mentioned task their EEG signal and heart rate will be measured. At the same time, participants will report on their subjective feeling of fatigue during these tasks. In addition, all participants will be administered cognitive tasks before and after the study, along with questionnaires. In the second and third experiments, tensiomyography and electromyography will also be recorded from the quadriceps muscle of the leg used for knee extension. Researchers will compare physiological and behavioural changes in response to specific neurotransmitter drug to answer the main question: what the role of a DA and a NA reuptake inhibitor on the onset of mental and physical fatigue is.

Conditions

Fatigue

Outcome Measures

Primary Outcomes (6)

• Number of repetitions

  Number of repetitions during knee extension task

  30 minutes

• Electroencephalography (spectral analysis)

  measurement of cortical activity with 64 channels (spectral density in alpha, beta, gamma, delta, theta)

  80 minutes

• Electroencephalography (event related potentials)

  measurement of cortical activity with 64 channels (event related potentials)

  80 minutes

• Electromyography

  Target muscles are rectus femoris and vastus lateralis (median frequency)

  60 minutes

• Accuracy

  Accuracy of correct answers during Stroop task

  60 minutes

• Reaction time

  Reaction time for answers during Stroop task

  60 minutes

Secondary Outcomes (11)

• Perceived stress scale questionnaire (PSS-10)

  5 minites

• the international physical activity questionnaire short form (IPAQ-SF)

  2 minutes

• The Brunel Mood Scale (BRUMS)

  5 minutes

• Motivation with visual analog score (Moti-VAS)

  1 minute

• The National Aeronautics and Space Administration Task Load Index (NASA-TLX)

  3 minutes

Study Arms (3)

Mental fatigue group

OTHER

Drug: Reboxetine Pill; Drug: Methylphenidate Oral Product

Physical fatigue group

OTHER

Drug: Reboxetine Pill; Drug: Methylphenidate Oral Product

Combined group

OTHER

Drug: Reboxetine Pill; Drug: Methylphenidate Oral Product

Interventions

Reboxetine Pill DRUG

8 mg

Combined group; Mental fatigue group; Physical fatigue group

Methylphenidate Oral Product DRUG

20 mg

Combined group; Mental fatigue group; Physical fatigue group

Eligibility Criteria

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

You may qualify if:

• Healthy trained individuals (exercises at least 1x per week, no neurological, cardiovascular internal or musculoskeletal disorders of any kind)
• No use of chronic or occasional prescribed medication (except for contraceptives)
• Non-smoker

You may not qualify if:

• Injuries of any kind in the past 6 months
• Pregnancy
• Specific food or drink allergies (e.g. lactose and/or gluten intolerance)
• Suffering from a chronic health condition (could be neurological, cardiovascular, internal and musculoskeletal)
• Participating in any concomitant care or research trials
• History of suffering from any mental/psychiatric disorders:
• Suffering from a higher risk of burn out, indicated by a total score of more than 2.59 on the Burn out assessment tool (BAT) Suffering from high general fatigue, indicated by a score of more than 57 on the Multidimensional fatigue inventory (MFI) Suffering from depression, indicated by a score of more than16 on the Beck depression inventory-II (BDI-II)
• Use of medication Chronic use with an exception for contraceptives Prescribed medication in between or before trials Use of non-prescribed occasional medication 24 hours prior each trial
• Use of caffeine and heavy efforts 24 hours prior each trial
• Suffering from colour vision deficiencies
• Not eating a standardized meal, the morning of each trial

Sponsors & Collaborators

• Vrije Universiteit Brussel: lead
• Science and Research Centre Koper: collaborator

Study Sites (1)

Brussels Labo voor Inspanning & Topsport U-residence

Brussels, Brussels Capital, 1050, Belgium

RECRUITING

Related Publications (1)

• Arauz YLA, Mali A, Lathouwers E, Habay J, Fortes LS, Meeusen R, Marusic U, De Pauw K, Roelands B. Distinct Roles of Dopamine and Noradrenaline in Physical Fatigue. Eur J Sport Sci. 2026 Feb;26(2):e70119. doi: 10.1002/ejsc.70119.

  PMID: 41601207 DERIVED

MeSH Terms

Conditions

Fatigue

Interventions

Reboxetine

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Yahaira Laurisa Arenales Arauz, Msc

CONTACT

+31615076269; laurisa.arenales@vub.be

Tjaša Ocvirk, Msc

CONTACT

+38631278074; tjasa.ocvirk@vub.be

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Yahaira Laurisa Arenales Arauz

Study Record Dates

• First Submitted: May 9, 2023
• First Posted: May 30, 2023
• Study Start: May 3, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: June 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)