Perfusion Augmentation Through Exercise

University of Zurich40 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Stroke, Ischemic

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: post-intervention (12 weeks)

Secondary Outcomes

Brain imaging - intravoxel incoherent motion (IVIM)

Functionality of brain microvasculature by measuring diffusion and perfusion components of tissue based on intravoxel incoherent motion

Time frame: post-intervention (12 weeks)

Brain imaging - NOVA-qMRI

Blood flow velocity based on non-invasive optimal vessel analysis quantitative magnetic resonance imaging

Time frame: post-intervention (12 weeks)

Brain imaging - Lesion volume

based on 3D T1 weighted imaging, 3D Fluid-Attenuated Inversion Recovery (FLAIR), Diffusion-Eighted Imaging (DWI)

Time frame: post-intervention (12 weeks)

Brain imaging - Collateral status

Collateral status based on 3D time of flight angiography (TOF)

Time frame: post-intervention (12 weeks)

Exercise stress testing

Cycle ergometer testing with spirometry

Time frame: post-intervention (12 weeks)

Six-Minute Walk Test (6MWT)

Functional walking capacity in meters