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NCT Number: NCT06292377

Better Understanding of Fatigue After STroke

Stroke is worldwide the second most common cause of death following heart attack and the leading cause of disability. Post-stroke fatigue (PSF) is a common complication after stroke and can be defined as 'an overwhelming exhaustion or tiredness, not related to exertion, which does not typically improve with rest'. Fatigue following stroke can be divided into early (< 3 months) and late (> 3 months) fatigue. PSF can have a considerable impact on a person's everyday activities and quality of life, participation in the rehabilitation process and levels of caregiver burden. Yet no efficient treatment exists to prevent or cure PSF because the pathophysiology remains unclear and seems to be multifaceted.

Autonomic dysfunction is a common complication after stroke, associated with higher morbidity and mortality. An easy tool to measure the function of the autonomic nervous system (ANS) is heart rate variability (HRV), which is defined as the beat-to-beat variation of the heart rate (= interbeat interval (IBI)). It is the result of alterations in the sympathetic and parasympathetic nervous system. In recent systematic reviews, authors stipulate that HRV can be regarded as a prognostic factor for short- and long-term stroke outcomes. HRV can be derived from 24 hours, 5 minutes (short-term) and < 5 minutes (ultra-short-term) measurements by applying time-domain and frequency-domain indices.

Autonomic dysfunction has been related to chronic fatigue syndrome, in addition to fatigue in multiple sclerosis, Parkinson's disease and myasthenia gravis. However, to the best of our knowledge, the relationship between autonomic dysfunction and PSF has not yet been fully investigated.

Fatigue is also common in cardiovascular diseases, especially in patients with heart failure (HF). HF can contribute to fatigue after stroke, independently of stroke.

Cardiac complications after acute ischemic stroke (AIS), such as arrhythmias, cardiac dysfunction and myocardial injury, are frequent. The so-called 'stroke-heart syndrome', a concept introduced in 2018, describes a broad spectrum of cardiac changes observed in 10-20% of patients with AIS within the first month after stroke onset, with a peak in the first 72 hours. A dysregulation in the neural-cardiac control after stroke is suspected to be the cause of the cascade leading to cardiac complications, in which autonomic dysfunction and inflammation seem to be part of the underlying mechanism.

Based on previous studies and by analogy with other neurological diseases, the investigators hypothesize that autonomic dysfunction following AIS contributes to PSF and that patients presenting heart failure as a complication following AIS have an increased risk of PSF.

To confirm this hypothesis, the investigators will conduct a prospective, interventional study where patients who are hospitalized at the Stroke Unit, within 72 hours after stroke symptom onset, will be included. Evaluation will take place of (a) the relationship between autonomic dysfunction (HRV) and early and late PSF, and of (b) the relationship between cardiac dysfunction and early PSF and late PSF.

There will also be an investigation into following elements:

* the association between early and late PSF and (a) certain inflammatory markers at admission (CRP, NLR), (b) stroke localization and (c) baseline imaging markers of brain frailty. * the role of pre-existing fatigue + pre-existing or post-stroke newly diagnosed cognitive impairment, depression and sleep disturbances on the course of PSF.

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Key information

Conditions

Stroke Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU Brugmann, Brussels, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 18
  • First-ever (suspicion of) ischemic stroke based on clinical examination and/or brain imaging
  • Onset < 72h at time of inclusion
  • Admitted at the stroke unit of CHU Brugmann and UZ Brussel
  • Ability to participate in assessment of fatigue, cognitive, mood and sleep disturbances
  • Ability to undergo MRI of the brain

Exclusion criteria

  • Unable to speak French or Dutch
  • Pre-existing stroke or other structural brain lesion
  • Life expectancy < 1 year
  • Severe language impairment or dementia impeding assessment of fatigue, cognitive, mood and sleep disturbances
  • Pregnancy or wish to become pregnant

Treatment and study plan

ECG

Diagnostic Test

An electrocardiogram (ECG) is a simple, non-invasive test that records the electrical activity of the heart.

Transthoracic echography (TTE)

Diagnostic Test

A transthoracic echocardiogram (TTE) is a test that uses ultrasound (sound waves) to create images of the heart.

Blood sampling

Diagnostic Test

Blood sampling will include: complete blood count, serum creatinine and electrolytes, liver enzymes, fast lipid profile, glucose, HbA1C, thyroid-stimulating hormone (TSH), CRP, iron status, cardiac troponin (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP).

Primary outcomes

  1. Heart rate variability (HRV)

    Time frame: Baseline (hospital admission)

    Heart rate variability is assessed by ECG monitoring and analyzed by means of Kubios software.

  2. Heart rate variability (HRV)

    Time frame: 3 months after baseline

    Heart rate variability is assessed by ECG monitoring and analyzed by means of Kubios software.

  3. Heart rate variability (HRV)

    Time frame: 12 months after baseline

    Heart rate variability is assessed by ECG monitoring and analyzed by means of Kubios software.

  4. Transthoracic echography (TTE)

    Time frame: Baseline (hospital admission)

    Cardiac function will be evaluated by a cardiologist with transthoracic echography (TTE).

  5. Transthoracic echography (TTE)

    Time frame: 3 months after baseline

    Cardiac function will be evaluated by a cardiologist with transthoracic echography (TTE).

  6. Transthoracic echography (TTE)

    Time frame: 12 months after baseline

    Cardiac function will be evaluated by a cardiologist with transthoracic echography (TTE).

  7. Fatigue Severity Scale (FSS-7)

    Time frame: 3 months after baseline

    The 7 items Fatigue Severity Scale (FSS-7) is a method of evaluating the impact of fatigue. The FSS-7 is a questionnaire with 7 statements rated from 1 (disagree) to 7 (agree). No official cut-off has been established, but most studies adopt the approach of using the average score: an average of ≥4 suggests clinically relevant fatigue, while an average <4 indicates low to moderate fatigue.

  8. Fatigue Severity Scale (FSS-7)

    Time frame: 12 months after baseline

    The 7 items Fatigue Severity Scale (FSS-7) is a method of evaluating the impact of fatigue. The FSS-7 is a questionnaire with 7 statements rated from 1 (disagree) to 7 (agree). No official cut-off has been established, but most studies adopt the approach of using the average score: an average of ≥4 suggests clinically relevant fatigue, while an average <4 indicates low to moderate fatigue.

  9. N-terminal pro-brain natriuretic peptide (NT-proBNP)

    Time frame: Baseline (hospital admission)

    NT-proBNP blood levels

  10. N-terminal pro-brain natriuretic peptide (NT-proBNP)

    Time frame: 3 months after baseline

    NT-proBNP blood levels

  11. N-terminal pro-brain natriuretic peptide (NT-proBNP)

    Time frame: 12 months after baseline

    NT-proBNP blood levels

  12. cardiac troponin (cTnT)

    Time frame: Baseline (hospital admission)

    cardiac troponin blood levels

  13. Non-Invasive Blood Pressure (NIBP)

    Time frame: Baseline (hospital admission)

    Non-invasive blood pressure (NIBP) is measured continuously using a Finapres device. Outcomes are recorded as real-time systolic, diastolic, and mean arterial pressure values.

  14. Non-Invasive Blood Pressure (NIBP)

    Time frame: 3 months after baseline

    Non-invasive blood pressure (NIBP) is measured continuously using a Finapres device. Outcomes are recorded as real-time systolic, diastolic, and mean arterial pressure values.

  15. Non-Invasive Blood Pressure (NIBP)

    Time frame: 12 months after baseline

    Non-invasive blood pressure (NIBP) is measured continuously using a Finapres device. Outcomes are recorded as real-time systolic, diastolic, and mean arterial pressure values.

  16. Baroreflex Sensitivity (BRS)

    Time frame: Baseline (hospital admission)

    Baroreflex Sensitivity (BRS) quantifies the autonomic regulation of blood pressure by measuring the change in heart rate in response to spontaneous fluctuations in blood pressure. It is calculated from continuous blood pressure and ECG recordings (using Finapres). BRS is expressed in ms/mmHg, with higher values indicating stronger baroreflex function.

  17. Baroreflex Sensitivity (BRS)

    Time frame: 3 months after baseline

    Baroreflex Sensitivity (BRS) quantifies the autonomic regulation of blood pressure by measuring the change in heart rate in response to spontaneous fluctuations in blood pressure. It is calculated from continuous blood pressure and ECG recordings (using Finapres). BRS is expressed in ms/mmHg, with higher values indicating stronger baroreflex function.

  18. Baroreflex Sensitivity (BRS)

    Time frame: 12 months after baseline

    Baroreflex Sensitivity (BRS) quantifies the autonomic regulation of blood pressure by measuring the change in heart rate in response to spontaneous fluctuations in blood pressure. It is calculated from continuous blood pressure and ECG recordings (using Finapres). BRS is expressed in ms/mmHg, with higher values indicating stronger baroreflex function.

Secondary outcomes

  1. Blood CRP level

    Time frame: Baseline (hospital admission)

    C-reactive protein (CRP) level in the blood (inflammatory marker)

  2. Blood neutrophil-to-lymphocyte ratio (NLR)

    Time frame: Baseline (hospital admission)

    The neutrophil-to-lymphocyte ratio (NLR), calculated by dividing the neutrophil count by the lymphocyte count, is an inflammatory marker.

  3. Stroke localization in the brain

    Time frame: Baseline (hospital admission)

    Manual segmentation of the acute ischemic lesion will be performed on the MRI of the brain

  4. Fazekas scale

    Time frame: Baseline (hospital admission)

    The Fazekas scale is a widely used method to visually rate hyperintense white matter signal abnormalities in magnetic resonance imaging (MRI) data. It ranges from 0 (no lesions) to 3.

  5. Global cortical atrophy scale

    Time frame: Baseline (hospital admission)

    Visual rating of cerebral atrophy on MRI images. Ranges from 0 (no lesions) to 39.

  6. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)

    Time frame: Baseline (hospital admission)

    The 26-item IQCODE questionnaire is completed by an informant to assess changes in cognitive function over the past 10 years in elderly individuals. Each item is rated on a 5-point scale from 1 (much improved) to 5 (much worse). The total score is calculated as the mean of all items, giving a range of 1-5. A mean score of ≥3.44 indicates significant cognitive decline.

  7. Presence for pre-existing fatigue (yes/no)

    Time frame: Baseline (hospital admission)

    Questionnaire (did you experience fatigue before you had your stroke' (yes/no))

  8. Duration of pre-existing fatigue

    Time frame: Baseline (hospital admission)

    Questionnaire ('how long did you experience fatigue' (< 1 week, < 3 months, 3-6 months and > 6 months)

  9. Patient Health Questionnaire-9 (PHQ-9)

    Time frame: Baseline (hospital admission)

    The PHQ-9 is a 9-item questionnaire assessing the frequency of depressive symptoms over the past two weeks. Each item is scored from 0 (not at all) to 3 (nearly every day), giving a total score range of 0-27. Total scores can be interpreted as follows:

    0-4: minimal or no depression 5-9: mild depression 10-14: moderate depression 15-19: moderately severe depression 20-27: severe depression

  10. Patient Health Questionnaire-9 (PHQ-9)

    Time frame: 3 months after baseline

    The PHQ-9 is a 9-item questionnaire assessing the frequency of depressive symptoms over the past two weeks. Each item is scored from 0 (not at all) to 3 (nearly every day), giving a total score range of 0-27. Total scores can be interpreted as follows:

    0-4: minimal or no depression 5-9: mild depression 10-14: moderate depression 15-19: moderately severe depression 20-27: severe depression

  11. Patient Health Questionnaire-9 (PHQ-9)

    Time frame: 12 months after baseline

    The PHQ-9 is a 9-item questionnaire assessing the frequency of depressive symptoms over the past two weeks. Each item is scored from 0 (not at all) to 3 (nearly every day), giving a total score range of 0-27. Total scores can be interpreted as follows:

    0-4: minimal or no depression 5-9: mild depression 10-14: moderate depression 15-19: moderately severe depression 20-27: severe depression

  12. Montreal Cognitive Assessment (MoCA) questionnaire

    Time frame: 3 months after baseline

    Questionnaire. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal.

  13. Montreal Cognitive Assessment (MoCA) score

    Time frame: 12 months after baseline

    Questionnaire.MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal.

  14. Insomnia Severity Index (ISI)

    Time frame: Baseline (hospital admission)

    Insomnia will be assessed by using the Insomnia Severity Index (ISI). The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).

  15. Insomnia Severity Index (ISI)

    Time frame: 3 months after baseline

    Insomnia will be assessed by using the Insomnia Severity Index (ISI). The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).

  16. Insomnia Severity Index (ISI)

    Time frame: 12 months after baseline

    Insomnia will be assessed by using the Insomnia Severity Index (ISI). The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).

  17. Complete blood count abnormalities: yes/no

    Time frame: Baseline (hospital admission)

    Clinical decision based on the analysis of the blood sample results

  18. Renal insufficiency: yes/no

    Time frame: Baseline (hospital admission)

    Clinical decision based on the analysis of the blood sample results

  19. Electrolyte imbalance: yes/no

    Time frame: Baseline (hospital admission)

    Clinical decision based on the analysis of the blood sample results

  20. Abnormal liver enzymes: yes/no

    Time frame: Baseline (hospital admission)

    Clinical decision based on the analysis of the blood sample results

  21. Dyslipidemia: yes/no

    Time frame: Baseline (hospital admission)

    Clinical decision based on the analysis of the blood sample results

  22. Diabetes: yes/no

    Time frame: Baseline (hospital admission)

    Clinical decision based on the analysis of the blood sample results

  23. Thyroid disorder: yes/no

    Time frame: Baseline (hospital admission)

    Clinical decision based on the analysis of the blood sample results

  24. Iron deficiency: yes/no

    Time frame: Baseline (hospital admission)

    Clinical decision based on the analysis of the blood sample results

  25. Epworth Sleepiness Scale (ESS)

    Time frame: Baseline (hospital admission)

    Description and scoring: the ESS is a questionnaire consisting of 8 daily-life situations in which the patient rates their likelihood of falling asleep on a scale from 0 (would never doze) to 3 (high chance of dozing).

    Total score = sum of the 8 items → possible range 0 to 24.

    Common interpretation:

    0-10: normal daytime sleepiness 11-24: excessive daytime sleepiness (higher score = greater sleepiness)

  26. Epworth Sleepiness Scale (ESS)

    Time frame: 3 months after baseline

    Description and scoring: the ESS is a questionnaire consisting of 8 daily-life situations in which the patient rates their likelihood of falling asleep on a scale from 0 (would never doze) to 3 (high chance of dozing).

    Total score = sum of the 8 items → possible range 0 to 24.

    Common interpretation:

    0-10: normal daytime sleepiness 11-24: excessive daytime sleepiness (higher score = greater sleepiness)

  27. Epworth Sleepiness Scale (ESS)

    Time frame: 12 months after baseline

    Description and scoring: the ESS is a questionnaire consisting of 8 daily-life situations in which the patient rates their likelihood of falling asleep on a scale from 0 (would never doze) to 3 (high chance of dozing).

    Total score = sum of the 8 items → possible range 0 to 24.

    Common interpretation:

    0-10: normal daytime sleepiness 11-24: excessive daytime sleepiness (higher score = greater sleepiness)

  28. Generalized Anxiety Disorder scale (GAD-7)

    Time frame: Baseline (hospital admission)

    Description and scoring: the GAD-7 is a 7-item questionnaire assessing symptoms of generalized anxiety over the past two weeks. Each item is scored from 0 (not at all) to 3 (nearly every day).

    Total score: sum of all 7 items → possible range 0-21.

    Common interpretation:

    0-4: minimal anxiety 5-9: mild anxiety 10-14: moderate anxiety 15-21: severe anxiety

  29. Generalized Anxiety Disorder scale (GAD-7)

    Time frame: 3 months after baseline

    Description and scoring: the GAD-7 is a 7-item questionnaire assessing symptoms of generalized anxiety over the past two weeks. Each item is scored from 0 (not at all) to 3 (nearly every day).

    Total score: sum of all 7 items → possible range 0-21.

    Common interpretation:

    0-4: minimal anxiety 5-9: mild anxiety 10-14: moderate anxiety 15-21: severe anxiety

  30. Generalized Anxiety Disorder scale (GAD-7)

    Time frame: 12 months after baseline

    Description and scoring: the GAD-7 is a 7-item questionnaire assessing symptoms of generalized anxiety over the past two weeks. Each item is scored from 0 (not at all) to 3 (nearly every day).

    Total score: sum of all 7 items → possible range 0-21.

    Common interpretation:

    0-4: minimal anxiety 5-9: mild anxiety 10-14: moderate anxiety 15-21: severe anxiety

Study contacts

Contact information is provided by the study sponsor or research team.

Anissa Ourtani, MD

CONTACT

[email protected]

3224754819

Sponsors and collaborators

Lead sponsor

Brugmann University Hospital

Other

Registry information

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Mar 5, 2024
Registry last updated
Mar 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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