Better Understanding of Fatigue After STroke

Stroke Clinical Trial

Official title:

Better Understanding of Fatigue After STroke

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06292377
• Other study ID #: BRUFAST
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 1, 2024
• Est. completion date: March 1, 2026

Study information

• Verified date: February 2024
• Source: Brugmann University Hospital
• Contact: Anissa Ourtani, MD
• Phone: 3224754819
• Email: Anissa.OURTANI[@]chu-brugmann.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 250
• Est. completion date: March 1, 2026
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, Dutch or English

• 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

Related Conditions & MeSH terms

• Stroke

Intervention

Diagnostic Test:
• ECG
An electrocardiogram (ECG) is a simple, non-invasive test that records the electrical activity of the heart.
• Transthoracic echography (TTE)
A transthoracic echocardiogram (TTE) is a test that uses ultrasound (sound waves) to create images of the heart.
• Blood sampling
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).

Locations

Country	Name	City	State
Belgium	UZ Brussel	Brussel
Belgium	CHU Brugmann	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Brugmann University Hospital

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heart rate variability (HRV)	Heart rate variability is assessed by ECG monitoring and analyzed by means of Kubios software.	Baseline (hospital admission)
Primary	Heart rate variability (HRV)	Heart rate variability is assessed by ECG monitoring and analyzed by means of Kubios software.	3 months after baseline
Primary	Heart rate variability (HRV)	Heart rate variability is assessed by ECG monitoring and analyzed by means of Kubios software.	12 months after baseline
Primary	Transthoracic echography (TTE)	Cardiac function will be evaluated by a cardiologist with transthoracic echography (TTE).	Baseline (hospital admission)
Primary	Transthoracic echography (TTE)	Cardiac function will be evaluated by a cardiologist with transthoracic echography (TTE).	3 months after baseline
Primary	Transthoracic echography (TTE)	Cardiac function will be evaluated by a cardiologist with transthoracic echography (TTE).	12 months after baseline
Primary	Fatigue Severity Scale	The Fatigue Severity Scale (FSS) is a method of evaluating the impact of fatigue. The FSS is a questionnaire with 9 statements rated from 1 (disagree) to 7 (agree). A total score of less than 36 suggests that the patient may not be suffering from fatigue. A total score of 36 or more suggests that the patient may need further evaluation by a physician.	Baseline (hospital admission)
Primary	Fatigue Severity Scale	The Fatigue Severity Scale (FSS) is a method of evaluating the impact of fatigue. The FSS is a questionnaire with 9 statements rated from 1 (disagree) to 7 (agree). A total score of less than 36 suggests that the patient may not be suffering from fatigue. A total score of 36 or more suggests that the patient may need further evaluation by a physician.	3 months after baseline
Primary	Fatigue Severity Scale	The Fatigue Severity Scale (FSS) is a method of evaluating the impact of fatigue. The FSS is a questionnaire with 9 statements rated from 1 (disagree) to 7 (agree). A total score of less than 36 suggests that the patient may not be suffering from fatigue. A total score of 36 or more suggests that the patient may need further evaluation by a physician.	12 months after baseline
Primary	N-terminal pro-brain natriuretic peptide (NT-proBNP)	NT-proBNP blood levels	Baseline (hospital admission)
Primary	N-terminal pro-brain natriuretic peptide (NT-proBNP)	NT-proBNP blood levels	3 months after baseline
Primary	N-terminal pro-brain natriuretic peptide (NT-proBNP)	NT-proBNP blood levels	12 months after baseline
Primary	cardiac troponin (cTnT)	cardiac troponin blood levels	Baseline (hospital admission)
Secondary	Blood CRP level	C-reactive protein (CRP) level in the blood (inflammatory marker)	Baseline (hospital admission)
Secondary	Blood neutrophil-to-lymphocyte ratio (NLR)	The neutrophil-to-lymphocyte ratio (NLR), calculated by dividing the neutrophil count by the lymphocyte count, is an inflammatory marker.	Baseline (hospital admission)
Secondary	Stroke localization in the brain	Manual segmentation of the acute ischemic lesion will be performed on the MRI of the brain	Baseline (hospital admission)
Secondary	Fazekas scale	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.	Baseline (hospital admission)
Secondary	Global cortical atrophy scale	Visual rating of cerebral atrophy on MRI images. Ranges from 0 (no lesions) to 39.	Baseline (hospital admission)
Secondary	Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)	Short questionnaire designed to assess cognitive decline and dementia in elderly people. A score of =3.44 on the IQCODE indicates cognitive decline.	Baseline (hospital admission)
Secondary	Presence for pre-existing fatigue (yes/no)	Questionnaire (did you experience fatigue before you had your stroke' (yes/no))	Baseline (hospital admission)
Secondary	Duration of pre-existing fatigue	Questionnaire ('how long did you experience fatigue' (< 1 week, < 3 months, 3-6 months and > 6 months)	Baseline (hospital admission)
Secondary	Patient Health Questionnaire-2 (PHQ-2)	The PHQ-2 inquires about the frequency of depressed mood and anhedonia (score from 0 to 6)	Baseline (hospital admission)
Secondary	Patient Health Questionnaire-2 (PHQ-2)	The PHQ-2 inquires about the frequency of depressed mood and anhedonia (score from 0 to 6)	3 months after baseline
Secondary	Patient Health Questionnaire-2 (PHQ-2)	The PHQ-2 inquires about the frequency of depressed mood and anhedonia (score from 0 to 6)	12 months after baseline
Secondary	Montreal Cognitive Assessment (MoCA) questionnaire	Questionnaire. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal.	3 months after baseline
Secondary	Montreal Cognitive Assessment (MoCA) score	Questionnaire.MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal.	12 months after baseline
Secondary	Insomnia Severity Index (ISI)	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).	Baseline (hospital admission)
Secondary	Insomnia Severity Index (ISI)	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).	3 months after baseline
Secondary	Insomnia Severity Index (ISI)	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).	12 months after baseline
Secondary	Complete blood count abnormalities: yes/no	Clinical decision based on the analysis of the blood sample results	Baseline (hospital admission)
Secondary	Renal insufficiency: yes/no	Clinical decision based on the analysis of the blood sample results	Baseline (hospital admission)
Secondary	Electrolyte imbalance: yes/no	Clinical decision based on the analysis of the blood sample results	Baseline (hospital admission)
Secondary	Abnormal liver enzymes: yes/no	Clinical decision based on the analysis of the blood sample results	Baseline (hospital admission)
Secondary	Dyslipidemia: yes/no	Clinical decision based on the analysis of the blood sample results	Baseline (hospital admission)
Secondary	Diabetes: yes/no	Clinical decision based on the analysis of the blood sample results	Baseline (hospital admission)
Secondary	Thyroid disorder: yes/no	Clinical decision based on the analysis of the blood sample results	Baseline (hospital admission)
Secondary	Iron deficiency: yes/no	Clinical decision based on the analysis of the blood sample results	Baseline (hospital admission)