How the brain contributes to mental and physical fatigue

Investigating Fundamental Mechanisms of Mental and Physical Fatigue Using Neurotransmitter Reuptake Inhibitors and Electroencephalography: a Randomized Counterbalanced Crossover Trial

Phase 3 Interventional Vrije Universiteit Brussel · NCT05880342

This trial tests whether two drugs that change brain chemicals—methylphenidate and reboxetine—alter how healthy, physically active adults feel and perform during mental and physical fatigue.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment62 (estimated)
Ages18 Years to 35 Years
SexAll
SponsorVrije Universiteit Brussel Academic / other
Locations1 site (Brussels, Brussels Capital)
Trial IDNCT05880342 on ClinicalTrials.gov

What this trial studies

Researchers will enroll healthy, trained adults and use a randomized, single-blind, placebo-controlled, counterbalanced crossover design to compare methylphenidate, reboxetine, and placebo across three experiments (physical fatigue, mental fatigue, and combined fatigue). During each session they will measure brain activation, fatigue perception, and neuromuscular efficiency with neurophysiological techniques before and after induced fatigue. The crossover design lets each participant serve as their own control to isolate drug effects on fatigue onset and brain activity. Participants with high baseline fatigue, burnout, psychiatric disorders, recent injuries, or certain medication use will be excluded to focus on healthy responses.

Who should consider this trial

Good fit: Ideal participants are healthy adults who exercise at least once weekly, are non-smokers, free of chronic health or psychiatric conditions, not taking medications (aside from contraceptives), and available for multiple lab visits in Brussels.

Not a fit: People with chronic fatigue disorders, active psychiatric illness, recent injuries, pregnancy, important food intolerances, smokers, or those already taking relevant medications are unlikely to benefit or qualify.

Why it matters

Potential benefit: If successful, the results could point to brain chemical targets for reducing perceived and performance-related fatigue and inform treatments for fatigue-related conditions.

How similar studies have performed: Prior research links dopamine and noradrenaline to fatigue and shows some benefit of stimulants in reducing fatigue in clinical settings, but applying these drugs to induced exercise and mental fatigue with detailed brain measures is relatively novel and evidence is mixed.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Where this trial is running

Brussels, Brussels Capital

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Fatigue
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.