Effect of Remote Ischemic Conditioning on Vascular Health in Stroke Patients

Study Overview
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Brief Summary
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The main aim of the current study is to assess cardiovascular effects of remote ischemic conditioning in patients who have suffered from stroke. A group of stroke patients will be subjected to four weeks of daily remote ischemic conditioning and four weeks of placebo and vascular function is assessed as a primary outcome.

Detailed Description
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Remote ischemic preconditioning (RIC) has been shown to reduce myocardial damage in association with a myocardial infarct but less is known about the potential effects on vascular function in patients who have suffered a stroke. RIC is a procedure by which blood flow to a limb is repeatedly occluded during a short period by an inflatable cuff. This project evaluates the effect of a two week period with RIC on vascular function and cerebral blood flow velocity as well as on factors associated with blood clot formation in patients who have suffered a stroke. The study also aims to provide mechanistic insight into the beneficial effects of the RIC procedure. Subjects are patients who within the past five years have suffered from lacunar infarct. The study is of a cross-over design with two weeks of homebased RIC treatment and two weeks of control period in a randomized order. Before and after the experimental periods the subjects undergo a number of tests assessing general health status, vascular function and cerebral blood flow velocity. Skeletal muscle samples are obtained for the determination of selected proteins related to vascular function and angiogenesis and blood samples are obtained for the determination of platelet function. .

Official Title
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Effect of Remote Ischemic Conditioning on Vascular Health in Stroke Patients

Conditions
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Stroke, Lacunar

Intervention / Treatment
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* Procedure: Remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical symptoms and corresponding computer tomographytomography/magnetic resonance (CT/MR)-scanning results for lacunar infarct within past five years. Small vessel disease stroke (lacunar infarct) is defined by the TOAST criteria Exclusion Criteria: Clinical significant carotid stenosis. Cardioembolic stroke Clinically significant chronic diseases other than lacunar infarct and associated factors Current or past smoker within the past ten years Current treatment with beta-blockers, peroral steroids or NSAIDS Alcohol- or drug-addiction. Pregnant or lactating. Inability to understand the content of the study information provided.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The patients will undergo two weeks of the intervention and two weeks of controlperiod, separated by three weeks. The intervention consists of inflating a cuff on the upperarm to 200 mmHg for 4 x 5 minutes, performed every day. The control period includes no specific intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remote ischemic conditioning<br>The participant will conduct remote ischemic preconditioning by use of an automated cuff device placed on the upper arm which inflates to 200 mmHg and occludes blood flow. The procedure is conducted on one arm 4 x 5 min per day. Each 5 min occlusion period is interspersed by 5 min. | Procedure: Remote ischemic conditioning<br>* Four weeks of daily ischemic conditioning and four weeks of sham ischemic conditioning in a cross over design<br>* Other names: Sham remote ischemic conditioning;|
| Sham Comparator: Sham occlusion<br>The participant will conduct a sham procedure of remote ischemic preconditioning by use of an automated cuff device placed on the upper arm which inflates minimally and does not occlude blood flow. The procedure is conducted on one arm 4 x 5 min per day. Each 5 min of sham occlusion is interspersed by 5 min. | Procedure: Remote ischemic conditioning<br>* Four weeks of daily ischemic conditioning and four weeks of sham ischemic conditioning in a cross over design<br>* Other names: Sham remote ischemic conditioning;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow mediated dilation | Assessment of brachial artery dilation after 5 min occlusion of upper arm by cuff | Change from baseline to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral vascular function-visual task | Assessment of change in cerebral blood flow velocity with visual task | Change from baseline to 4 weeks | 
| Cerebral vascular function- motorparadigm task | Assessment of change in cerebral blood flow velocity with motorparadigm task | Change from baseline to 4 weeks | 
| Skeletal muscle blood flow | Femoral arterial blood flow measured at rest and during one leg knee extensor exercise | Change from baseline to 4 weeks | 
| Platelet reactivity | Platelet reactivity is assessed in platelets isolated from blood samples | Change from baseline to 4 weeks | 
| Blood clot structure-gel point | Blood clot structure is assessed by gel point | Change from baseline to 4 weeks | 
| Blood clot structure-fractal analysis | Blood clot structure is assessed by fractal analysis | Change from baseline to 4 weeks | 
| Skeletal muscle proteins | Proteins associated with angiogenesis and vascular function are assessed in skeletal muscle samples obtained from the thigh muscle | Change from baseline to 4 weeks | 
| Plasma proteins | Protein amount is determined in plasma | Change from baseline to 4 weeks | 
| Plasma lipids | Lipid concentration is determined in plasma | Change from baseline to 4 weeks | 
| Oral glucose tolerance test (OGTT) | An oral glucose tolerance test is conducted by assesment of blood glucose and insulin before and after ingestion of glucose | Change from baseline to 4 weeks | 
| Body composition | Body composition is assessed by dual energy x-ray absorptiometry | Change from baseline to 4 weeks |