StrokePhase 3MODEXNCT06354985
Modafinil and Exercise for Post Stroke Fatigue
A Phase 3 study testing Modafinil 200mg and Exercise in people with Stroke and Fatigue, run by University Health Network, Toronto.
Trial summary
A stroke happens when blood flow to the brain is stopped and the brain gets damaged. At least half of people with a stroke have fatigue months and even years later. A lot of people report fatigue as one of the worst symptoms post stroke that can affect daily activities and the length and quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Modafinil 200mg and Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 212 participants
- Where
- No sites listed yet
- Study dates
- Sep 2025to Sep 2027
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >18 years of age (on date of consent)
- >3 months post stroke onset (i.e. intracerebral hemorrhage or ischemic stroke diagnosed by a physician) (on date of consent)
- evidence of stroke on computed tomography (CT) or magnetic resonance imaging (MRI)
- disabling post stroke fatigue as measured by Multidimensional Fatigue Inventory score >60
- Modified Rankin disability score <4
- Able to participate in moderate exercise for an hour (with one person assistance or less)
Who cannot join
- contraindications to Modafinil
- on stimulant medications already
- subarachnoid hemorrhage
- impaired comprehension or language impairment that prevents following visual or pictograph adapted instructions or providing informed consent
- severe motor impairment or inability to participate in the exercise
- unable to participate in exercise due to musculoskeletal complaints, unstable heart failure, or renal disease
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- untreated hypothyroidism or anemia
- cancer likely to result in death in <6 months
- severe depression requiring therapy as indicated by suicidal ideation and/or Depression Anxiety Stress Scales (DASS) depression sub-score >20
- currently enrolled in a structured exercise program
- untreated severe sleep apnea with an Apnea/Hypopnea index >30 as measured by validated wearable sleep apnea detector
- pregnant, breastfeeding, or positive test for pregnancy at baseline
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Modafinil and Exercise for Post Stroke Fatigue (MODEX)
A stroke happens when blood flow to the brain is stopped and the brain gets damaged. At least half of people with a stroke have fatigue months and even years later. A lot of people report fatigue as one of the worst symptoms post stroke that can affect daily activities and the length and quality of life. Though all the reasons for fatigue after stroke and how to best treat it are not fully understood, the investigators think that fatigue results from the stroke changing the brain, reducing physical fitness, and decreasing muscle strength. A stroke can also affect sleep and mood, which can impact how people feel too. It is also not known why women experience more fatigue than men after a stroke.
Some studies have tested a drug called Modafinil for post stroke fatigue, while other studies have tested exercise for it. Yet, there is unclear evidence for either treatment, so this study has the following aim:
Read more
- Test if Exercise plus Modafinil is better than Exercise plus a Sugar Pill
This study will take place at up to 6 Canadian research sites to give a good representation of people after a stroke. Each person will be tested on fatigue, mood, fitness, thinking skills, sleep, and usual activity levels.
Participants will be assigned at random (like flipping a coin) to 1 of 2 groups:
- Sugar Pill plus Exercise
- Modafinil plus Exercise
The treatment will last 8 weeks. The Modafinil or Sugar Pill will be taken once a day. The exercise will be delivered virtually by a trained therapist over computer to people at home 3 times a week. Change in fatigue, quality of life, and other outcomes will be measured over 6 months.
The investigators will assess the results to identify the best treatment for post stroke fatigue and hope to be able to find a treatment that will help reduce fatigue and improve quality of life after a stroke.
Read the detailed description
Study Rationale Post stroke fatigue (PSF) afflicts as many as 70% of the 400,000 Canadians with stroke. People with stroke endorse PSF as the most serious unmet research priority. Pathological fatigue is not relieved by rest and is characterized by persistent or extreme tiredness, exhaustion, and/or difficulty in initiating or sustaining voluntary activities. PSF is an excellent exemplar to study as the cause of disabling PSF is unclear. Systematic reviews confirm that PSF is multifactorial having both peripheral (e.g. cardiovascular and neuromuscular) and central (e.g. alterations in brain function resulting in both physical and psychological symptoms) components. There are no evidence-based treatments for PSF, however, exercise and the dopaminergic medication Modafinil that targets the dopaminergic movement circuits in the brain, have shown promise in alleviating symptoms in small studies.
Study Design This multicentre clinical trial will involve a double blind randomized controlled trial design to quantify the effect of a structured exercise program combined with Modafinil 200 mg daily or placebo medication over 8 weeks on severity of fatigue symptoms. It aims to recruit 212 participants into one of two arms. It will also explore the interactions of Modafinil in combination with exercise. The effects of mood, sleep, stroke impairments, sex, gender and activity levels on post stroke fatigue will also be explored.
Study Population Study participants must meet the inclusion/exclusion criteria at the time of entry into the study. In general, participants will be >3 months post stroke onset (i.e. intracerebral hemorrhage or ischemic stroke diagnosed by a physician) at the time of consent into the study.
Primary Hypothesis The primary hypothesis based on outcomes at 8 weeks is that structured telerehabilitation fitness and strengthening exercise plus Modafinil will improve fatigue symptom severity more than placebo medication and the same exercise.
- Being tested
- Modafinil 200mg, Placebo, Exercise
- Medical subject headings
- Stroke, Fatigue, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modafinil 200mgDrug
Also called Modafinil
Modafinil 200mg daily for 8 weeks.
PlaceboDrug
Also called Sugar Pill
Placebo daily for 8 weeks.
ExerciseBehavioural
Exercise three times per week for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo Drug + Exercise | Placebo comparator | Placebo Drug + Exercise for 8 weeks. Receives: Drug: Placebo; Behavioral: Exercise |
| Modafinil 200 mg/day + Exercise | Active comparator | Modafinil 200 mg/day + Exercise for 8 weeks. Receives: Drug: Modafinil 200mg; Behavioral: Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of Fatigue Symptoms
Multidimensional Fatigue Inventory
Measured: Week 8
Secondary outcomes (10)
Severity of Fatigue Symptoms
Multidimensional Fatigue Inventory
Measured: Week 4 and 26
Impact on Quality of Life
Medical Outcomes Short Form Scale
Measured: Week 8 and 26
Walking Recovery
Timed Up and Go
Measured: Week 8 and 26
Leg Strength and Coordination
30-Second Sit to Stand Test
Measured: Week 8 and 26
3-Day Physical Activity Assessment
Activity Accelerometer
Measured: Week 8
Mood and Anxiety
Depression Anxiety Stress Scales
Measured: Week 4, 8, and 26
Attention
Montreal Cognitive Assessment
Measured: Week 8 and 26
Cognition
Trails Tests
Measured: Week 8 and 26
Health Resource Utilization
Health Resource Utilization Questionnaire
Measured: Week 4, 8, and 26
Quality Adjusted Life Years
Cost Per Quality Adjusted Life Years
Measured: Week 4, 8, and 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2024
- Study startSep 2025 (estimated)
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 212 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Bayley, MD, FRCPC, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06354985
- Sponsor's protocol ID
- 23-5996
- Other IDs
- MODEX2023, FRN:183960, CTO Project ID: 4701
- Acronym
- MODEX
- Status last verified
- Jun 2025
- First submitted
- 22 Mar 2024
- Last updated
- 10 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modafinil and Exercise for Post Stroke Fatigue (MODEX)
- ClinicalTrials.gov ID
- NCT06354985
- Acronym / sponsor ID
- MODEX / 23-5996
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 212 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Sep 2025 (estimated)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 9 Apr 2024 (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.
A stroke happens when blood flow to the brain is stopped and the brain gets damaged. At least half of people with a stroke have fatigue months and even years later. A lot of people report fatigue as one of the worst symptoms post stroke that can affect daily activities and the length and quality of life. Though all the reasons for fatigue after stroke and how to best treat it are not fully understood, the investigators think that fatigue results from the stroke changing the brain, reducing physical fitness, and decreasing muscle strength. A stroke can also affect sleep and mood, which can impact how people feel too. It is also not known why women experience more fatigue than men after a stroke.
Some studies have tested a drug called Modafinil for post stroke fatigue, while other studies have tested exercise for it. Yet, there is unclear evidence for either treatment, so this study has the following aim:
- Test if Exercise plus Modafinil is better than Exercise plus a Sugar Pill
This study will take place at up to 6 Canadian research sites to give a good representation of people after a stroke. Each person will be tested on fatigue, mood, fitness, thinking skills, sleep, and usual activity levels.
Participants will be assigned at random (like flipping a coin) to 1 of 2 groups:
- Sugar Pill plus Exercise
- Modafinil plus Exercise
The treatment will last 8 weeks. The Modafinil or Sugar Pill will be taken once a day. The exercise will be delivered virtually by a trained therapist over computer to people at home 3 times a week. Change in fatigue, quality of life, and other outcomes will be measured over 6 months.
The investigators will assess the results to identify the best treatment for post stroke fatigue and hope to be able to find a treatment that will help reduce fatigue and improve quality of life after a stroke.
Detailed description
Study Rationale Post stroke fatigue (PSF) afflicts as many as 70% of the 400,000 Canadians with stroke. People with stroke endorse PSF as the most serious unmet research priority. Pathological fatigue is not relieved by rest and is characterized by persistent or extreme tiredness, exhaustion, and/or difficulty in initiating or sustaining voluntary activities. PSF is an excellent exemplar to study as the cause of disabling PSF is unclear. Systematic reviews confirm that PSF is multifactorial having both peripheral (e.g. cardiovascular and neuromuscular) and central (e.g. alterations in brain function resulting in both physical and psychological symptoms) components. There are no evidence-based treatments for PSF, however, exercise and the dopaminergic medication Modafinil that targets the dopaminergic movement circuits in the brain, have shown promise in alleviating symptoms in small studies.
Study Design This multicentre clinical trial will involve a double blind randomized controlled trial design to quantify the effect of a structured exercise program combined with Modafinil 200 mg daily or placebo medication over 8 weeks on severity of fatigue symptoms. It aims to recruit 212 participants into one of two arms. It will also explore the interactions of Modafinil in combination with exercise. The effects of mood, sleep, stroke impairments, sex, gender and activity levels on post stroke fatigue will also be explored.
Study Population Study participants must meet the inclusion/exclusion criteria at the time of entry into the study. In general, participants will be >3 months post stroke onset (i.e. intracerebral hemorrhage or ischemic stroke diagnosed by a physician) at the time of consent into the study.
Primary Hypothesis The primary hypothesis based on outcomes at 8 weeks is that structured telerehabilitation fitness and strengthening exercise plus Modafinil will improve fatigue symptom severity more than placebo medication and the same exercise.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo Drug + Exercise | Placebo comparator | Drug: Placebo, Behavioral: ExercisePlacebo Drug + Exercise for 8 weeks. |
| Modafinil 200 mg/day + Exercise | Active comparator | Drug: Modafinil 200mg, Behavioral: ExerciseModafinil 200 mg/day + Exercise for 8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- >18 years of age (on date of consent)
- >3 months post stroke onset (i.e. intracerebral hemorrhage or ischemic stroke diagnosed by a physician) (on date of consent)
- evidence of stroke on computed tomography (CT) or magnetic resonance imaging (MRI)
- disabling post stroke fatigue as measured by Multidimensional Fatigue Inventory score >60
- Modified Rankin disability score <4
Key exclusion criteria (12 listed)
- contraindications to Modafinil
- on stimulant medications already
- subarachnoid hemorrhage
- impaired comprehension or language impairment that prevents following visual or pictograph adapted instructions or providing informed consent
- severe motor impairment or inability to participate in the exercise
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 |
|---|---|---|
| Modafinil 200mgAlso: ModafinilModafinil 200mg daily for 8 weeks. | Drug | Modafinil 200 mg/day + Exercise |
| PlaceboAlso: Sugar PillPlacebo daily for 8 weeks. | Drug | Placebo Drug + Exercise |
| ExerciseExercise three times per week for 8 weeks. | Behavioural | Modafinil 200 mg/day + Exercise, Placebo Drug + Exercise |
Primary outcome
Severity of Fatigue Symptoms
Time frame: Week 8
Multidimensional Fatigue Inventory
10 secondary outcomes
Severity of Fatigue Symptoms
Time frame: Week 4 and 26
Impact on Quality of Life
Time frame: Week 8 and 26
Walking Recovery
Time frame: Week 8 and 26
Leg Strength and Coordination
Time frame: Week 8 and 26
3-Day Physical Activity Assessment
Time frame: Week 8
Mood and Anxiety
Time frame: Week 4, 8, and 26
Attention
Time frame: Week 8 and 26
Cognition
Time frame: Week 8 and 26
Health Resource Utilization
Time frame: Week 4, 8, and 26
Quality Adjusted Life Years
Time frame: Week 4, 8, and 26
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 10 Jun 2025.
- Individual participant dataSharing planned: No
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OPTION-EMEA Clinical Trial
Atrial Fibrillation (AF), Stroke Prevention in Patients With Atrial Fibrillation
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Metformin in Acute Ischemic Stroke
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Music Therapy in Post-Stroke Patients: A Clinical Trial
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Detecting and Predicting Post-stroke Cognitive Impairment Using the Oxford Cognitive Screen
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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.
Mark Bayley, MD, FRCPC principal investigator
University Health Network, Toronto
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Modafinil 200mg and Exercise in people with Stroke and Fatigue, run by University Health Network, Toronto.
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 12 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: opening soon, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
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.
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 Josie Chundamala, MA, CCRP (416-597-7015, josie.chundamala@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severity of Fatigue Symptoms (time frame: Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jun 2025.