Perfusion Augmentation Through Exercise

Stroke, Ischemic Clinical Trial

— PERFEX  

Official title:

Changes in PERFusion and Cerebrovascular Reactivity Through Aerobic EXercise Training After Ischemic Stroke - a Proof of Concept Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05584605
• Other study ID #: 2022-00438
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 2022
• Est. completion date: December 2024

Study information

• Verified date: October 2022
• Source: University of Zurich
• Contact: Anne Schwarz, PhD
• Phone: +41442555645
• Email: anne.schwarz[@]usz.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Large cerebral vessel occlusion is a common phenomenon in the general population and accounts for 13-35% of ischemic strokes. Chronic stenosis in the large cerebral arteries is associated with cerebral hypoperfusion, cognitive decline and an increased risk of stroke or recurrent stroke, respectively.

Even with upgrowth of surgical or endovascular interventions, mechanical reopening of the occluded vessels is often not possible. Alternative treatment opportunities include minimal-to-moderate blood pressure elevation (typically by ceasing antihypertensives) waiting for collateral circulation to develop spontaneously. Another conservative approach to increase cerebral perfusion is aerobic exercising. Physical activity has shown to lead to cerebral blood flow increase, especially in activated brain areas of healthy human and rat models. However, it is remains unknown, how physiological adaptation to physical activity expresses in persons after stroke due to large vessel occlusion. Herein, it is hypothesized that aerobic exercise facilitates the development of an extensive and functional vascular collateral network in persons with ischemic stroke and perfusion compromise.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and Female patients of 18 years of age or above

• Subjects after ischemic cerebral stroke (= 3 months) due to large vessel occlusion

• Subjects do not qualify for flow augmentation through ECIC bypass or endovascular treatment

• Persistent deficit in BOLD-CVR

• Functional Ambulatory Categories >2

• Discharged from hospitalization / inpatient rehabilitation

• Living independent before stroke (mRS =3)

• Written Informed Consent

Exclusion Criteria:

• Severe cardiac disease, such as instable angina pectoris, pericarditis, heart failure (New York Health Association > II°), or hemodynamically significant valvular dysfunction

• Complete arterial stenosis

• Peripheral artery disease with mild to moderate claudication at < 200m or 200-1000m of walking

• Contra-indication, such as a history of a seizure, prior electroconvulsive therapy, deep brain stimulators or other metal in the head, skull defect, pacemaker, neuroleptic medication

• Inability to follow the procedures of the study, e.g., due to language problems (unable to follow to stage commands), psychological disorders (major depression), and / or a neurodegenerative disease (dementia)

• Known or suspected non-compliance, documented drug, or alcohol abuse

• Pregnancy

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke, Ischemic

Intervention

Behavioral:
• Aerobic treadmill training
The intervention will be delivered based on the initial exercise testing and graded based by increasing the duration, speed and/or altitude of the treadmill training.
• Stretching exercise
Interventions, such as stretching, relaxation, passive soft-tissue technics (excl. manipulation) that do not elevate the heart rate above 20HRR

Locations

Country	Name	City	State
Switzerland	Ambulante Reha Triemli Zu¨rich	Zürich
Switzerland	Klinik Lengg AG	Zürich
Switzerland	University Hospital Zurich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Concomitant medications	covariate	post-intervention (12 weeks) + follow-up (+3 months)
Primary	Brain imaging - cerebrovascular reactivity (CVR) by BOLD-fMRI	Functional brain tissue perfusion and tissue at risk based on cerebrovascular reactivity by blood oxygenation-level dependent functional magnetic resonance imaging (BOLD-fMRI), measured as the percentage BOLD signal change /mmHg CO2.	post-intervention (12 weeks)
Secondary	Brain imaging - intravoxel incoherent motion (IVIM)	Functionality of brain microvasculature by measuring diffusion and perfusion components of tissue based on intravoxel incoherent motion	post-intervention (12 weeks)
Secondary	Brain imaging - NOVA-qMRI	Blood flow velocity based on non-invasive optimal vessel analysis quantitative magnetic resonance imaging	post-intervention (12 weeks)
Secondary	Brain imaging - Lesion volume	based on 3D T1 weighted imaging, 3D Fluid-Attenuated Inversion Recovery (FLAIR), Diffusion-Eighted Imaging (DWI)	post-intervention (12 weeks)
Secondary	Brain imaging - Collateral status	Collateral status based on 3D time of flight angiography (TOF)	post-intervention (12 weeks)
Secondary	Exercise stress testing	Cycle ergometer testing with spirometry	post-intervention (12 weeks)
Secondary	Six-Minute Walk Test (6MWT)	Functional walking capacity in meters	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	Ten-Meter Walk Test (10MWT)	Walking speed in m/s	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	Fugl-Meyer Assessment of the Lower Extremity (FMMA-LE)	Stroke-specific motor impairment index to assess lower limb motor function with a total score ranging from 0 to 34 and higher scores indicating better performance.	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	Motricity Index of the Lower Extremity (MI-LE)	Muscle strength assessment of three major muscle groups of the lower extremity with a total score ranging from 0 to 100 and higher scores indicating better performance.	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	5-Chair-Rise-Test	Functional muscle strength, measured in seconds to complete the task.	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	International Physical Activity Questionnaire (IPAQ)	self-reported physical activity	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	Montreal Cognitive Assessment (MoCA)	Screening assessment of cognitive functions with a maximum score of 30 points.	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	Word list learning	Assessment of memory function	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	Digit Span Test / Corsi block	Assessment verbal and nonverbal working memory	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	Stroop test	Assessment of executive function and inhibition	post-intervention (12 weeks) + follow-up (+3 months)
Secondary	European Quality of Life 5 Dimensions 5 Level (5Q-5D-5L)	Quality of life questionnaire that assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) on a 5-level scale ranging from 1 - no, 2 - slight, 3 - moderate, 4 - severe to 5 - extreme problems or unstable to.	post-intervention (12 weeks) + follow-up (+3 months)