FatiguePhase 3NCT05880342
The Role of the Brain in Mental and Physical Fatigue
A Phase 3 study testing Reboxetine Pill and Methylphenidate Oral Product in people with Fatigue, run by Vrije Universiteit Brussel at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Fatigue
- What is being tested?
- Reboxetine Pill and Methylphenidate Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteBelgium
- Study dates
- 3 May 2023to 31 Dec 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- 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
Who cannot join
- 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:
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
Brussels Labo voor Inspanning & Topsport U-residence
Brussels, Brussels Capital, 1050
+32 (0)2 629 22 22
About this study
Official title: Investigating Fundamental Mechanisms of Mental and Physical Fatigue Using Neurotransmitter Reuptake Inhibitors and Electroencephalography: a Randomized Counterbalanced Crossover Trial
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:
Read more
- 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
- Being tested
- Reboxetine Pill, Methylphenidate Oral Product
- Medical subject headings
- Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reboxetine PillDrug
8 mg
Methylphenidate Oral ProductDrug
20 mg
| Study group | Role | What they receive |
|---|---|---|
| Mental fatigue group | Other | Not described Receives: Drug: Reboxetine Pill; Drug: Methylphenidate Oral Product |
| Physical fatigue group | Other | Not described Receives: Drug: Reboxetine Pill; Drug: Methylphenidate Oral Product |
| Combined group | Other | Not described Receives: Drug: Reboxetine Pill; Drug: Methylphenidate Oral Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of repetitions
Number of repetitions during knee extension task
Measured: 30 minutes
Electroencephalography (spectral analysis)
measurement of cortical activity with 64 channels (spectral density in alpha, beta, gamma, delta, theta)
Measured: 80 minutes
Electroencephalography (event related potentials)
measurement of cortical activity with 64 channels (event related potentials)
Measured: 80 minutes
Electromyography
Target muscles are rectus femoris and vastus lateralis (median frequency)
Measured: 60 minutes
Accuracy
Accuracy of correct answers during Stroop task
Measured: 60 minutes
Reaction time
Reaction time for answers during Stroop task
Measured: 60 minutes
Secondary outcomes (11)
Perceived stress scale questionnaire (PSS-10)
Result is the score of the questionnaire (may 40 points)
Measured: 5 minites
the international physical activity questionnaire short form (IPAQ-SF)
Result is the score of the questionnaire
Measured: 2 minutes
The Brunel Mood Scale (BRUMS)
Result is the score of the questionnaire (each subscale max 0-16)
Measured: 5 minutes
Motivation with visual analog score (Moti-VAS)
Result is the score between 0 and 100
Measured: 1 minute
The National Aeronautics and Space Administration Task Load Index (NASA-TLX)
Result is the score of the questionnaire
Measured: 3 minutes
Subjective feeling of Mental Fatigue with visual analog score (M-VAS)
Result is the score between 0 and 100
Measured: 1 minute
Subjective feeling of physical fatigue with visual analog score (P-VAS)
Result is the score between 0 and 100
Measured: 1 minute
Karolinska Sleepiness Scale (KSS)
Result is the score of the questionnaire (max 24)
Measured: 5 minutes
Internal load of the physical performance (CR100 RPE)
Result is the score between 0 and 100
Measured: 30 minutes
Heart Rate
continuously assessed by using the POLAR H10 sensor
Measured: 60 minutes
Lactate concentration
blood lactate will be measured at the beginning and end of the trial at the finger tip of the participant (unit = mmol/L)
Measured: 5 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2023
- Study start3 May 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for FatigueStudies of the same condition, open and under way.
- More trials run by Vrije Universiteit BrusselThe 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 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vrije Universiteit Brussel
- Sponsor type
- University, hospital or other
- Collaborators
- Science and Research Centre Koper
- Responsible party
- Principal investigator, Yahaira Laurisa Arenales Arauz, Vrije Universiteit Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05880342
- Sponsor's protocol ID
- G095422N
- Status last verified
- Jun 2025
- First submitted
- 9 May 2023
- Last updated
- 18 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Arenales Arauz YL, Omejc N, Diaz MA, Habay J, Vanderborght B, De Pauw K, Roelands B, Marusic U. Catecholaminergic Contributions to Inhibitory Control Following Physical Fatigue: Behavioral and Neurophysiological Findings. Eur J Sport Sci. 2026 Sep;26(9):e70231. doi: 10.1002/ejsc.70231.
PubMed 42608643Arauz 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.
PubMed 41601207
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Fundamental Mechanisms of Mental and Physical Fatigue Using Neurotransmitter Reuptake Inhibitors and Electroencephalography: a Randomized Counterbalanced Crossover Trial
- ClinicalTrials.gov ID
- NCT05880342
- Acronym / sponsor ID
- G095422N
- Conditions
- Fatigue
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Vrije Universiteit BrusselUniversity, hospital or other
- Collaborators
- Science and Research Centre Koper
- Study start
- 3 May 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 30 May 2023 (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 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| Reboxetine Pill8 mg | Drug | Combined group, Mental fatigue group, Physical fatigue group |
| Methylphenidate Oral Product20 mg | Drug | Combined group, Mental fatigue group, Physical fatigue group |
Primary outcome
Number of repetitions
Time frame: 30 minutes
Number of repetitions during knee extension task
Electroencephalography (spectral analysis)
Time frame: 80 minutes
measurement of cortical activity with 64 channels (spectral density in alpha, beta, gamma, delta, theta)
Electroencephalography (event related potentials)
Time frame: 80 minutes
measurement of cortical activity with 64 channels (event related potentials)
Electromyography
Time frame: 60 minutes
Target muscles are rectus femoris and vastus lateralis (median frequency)
Accuracy
Time frame: 60 minutes
Accuracy of correct answers during Stroop task
Reaction time
Time frame: 60 minutes
Reaction time for answers during Stroop task
11 secondary outcomes
Perceived stress scale questionnaire (PSS-10)
Time frame: 5 minites
the international physical activity questionnaire short form (IPAQ-SF)
Time frame: 2 minutes
The Brunel Mood Scale (BRUMS)
Time frame: 5 minutes
Motivation with visual analog score (Moti-VAS)
Time frame: 1 minute
The National Aeronautics and Space Administration Task Load Index (NASA-TLX)
Time frame: 3 minutes
Subjective feeling of Mental Fatigue with visual analog score (M-VAS)
Time frame: 1 minute
Subjective feeling of physical fatigue with visual analog score (P-VAS)
Time frame: 1 minute
Karolinska Sleepiness Scale (KSS)
Time frame: 5 minutes
Internal load of the physical performance (CR100 RPE)
Time frame: 30 minutes
Heart Rate
Time frame: 60 minutes
Lactate concentration
Time frame: 5 minutes
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2025.
- Derived from this study: PubMed 42608643Arenales Arauz YL, Omejc N, Diaz MA, Habay J, Vanderborght B, De Pauw K, Roelands B, Marusic U. Catecholaminergic Contributions to Inhibitory Control Following Physical Fatigue: Behavioral and Neurophysiological Findings. Eur J Sport Sci. 2026 Sep;26(9):e70231. doi: 10.1002/ejsc.70231.
- Derived from this study: PubMed 41601207Arauz 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.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Reboxetine Pill and Methylphenidate Oral Product in people with Fatigue, run by Vrije Universiteit Brussel at 1 site in Belgium.
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 11 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: looking for participants now, as of the sponsor's last update on 18 Jun 2025. 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 Belgium. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yahaira Laurisa Arenales Arauz, Msc (+31615076269, laurisa.arenales@vub.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of repetitions (time frame: 30 minutes). The study lists 6 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 NCT05880342, which also lists 2 linked publications.
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 18 Jun 2025.