Clinical Trial on Remote Ischemic Preconditioning and Cerebral Small Vessel Disease

Study Overview
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Brief Summary
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The hypothesis of this study is that remote ischemic preconditioning (RIPC) might have a beneficial effect on outcomes of cerebral small vessel disease (CSV).

Detailed Description
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CSV constitutes an important type of ischemic stroke due to a generalized hypo-perfusion of brain. Few treatment methods are available except some beneficial effect shown with nimodipine. The potential treatment effect of RIPC on protection of brain from cerebral small vessel disease has not been investigated. The investigators designed this randomized, double-blind, controlled clinical trial to examine (1) whether RIPC has a beneficial effect on brain lesions of CSV, and (2) whether RIPC can protect patients of CSV from cognitive deterioration. There are 2 arms in this trial: One arm is RIPC treatment, the other one is sham RIPC treatment. Brain lesions will be quantified by volumetric MRI, and Xe-CT will be used to evaluate cerebral blood perfusion. Cognitive function will be evaluated by mini-mental state examination (MMSE) and the Montreal Cognitive Assessment (MoCA).

Official Title
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A Random Controlled, Double-Blind Clinical Trial: Remote Ischemic Preconditioning and Cerebral Small Vessel Disease

Conditions
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Cerebral Small Vessel Disease

Intervention / Treatment
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* Procedure: remote ischemic preconditioning
* Procedure: sham remote ischemic preconditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 40-80 years; Ischemic cerebrovascular event onset, if any, must be within 6 months; TCD and carotid ultrasound exclude vascular narrow that can cause hemodynamic changes (usually >50% narrow lumen); MRI confirmed the presence of lacunar infarction and / or generalized white matter lesions; Written consent was obtained from the subject. Exclusion Criteria: History of intracranial hemorrhage; Significant bleeding from other parts of the body; History of atrial fibrillation; History of myocardial infarction within six months; Moyamoya disease or vasculitis; Hereditary small vessel disorders, such as CADASIL, FABRY, and mitochondrial encephalo-myopathy; Significant bleeding-coagulation dysfunction; Abnormal blood pressure, glucose and/or lipids after restrict treatment regimen; Severe liver/kidney disease, cancer or critical illness of internal medicine and surgery.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: remote ischemic preconditioning<br>Receiving remote ischemic preconditioning (RIPC) treatment with pressure set at 200 mmHg. | Procedure: remote ischemic preconditioning<br>* RIPC consists of five 5-min cycles of right upper arm ischemia/reperfusion, induced by an automated cuff-inflator placed on the right upper arm which is inflated to 200 mmHg for 5mins followed by deflating the cuff for 5mins, each patient in the RIPC group will have the treatment twice a day for two weeks.<br>|
| Sham Comparator: placebo remote ischemic preconditioning<br>Receiving sham RIPC treatment with pressure set at 50 mmHg | Procedure: sham remote ischemic preconditioning<br>* Sham RIPC consists of five 5-min cycles of right upper arm ischemia/reperfusion, induced by an automated cuff-inflator placed on the right upper arm which is inflated to 50 mmHg for 5mins followed by deflating the cuff for 5mins, each patient in the placebo RIPC group will have the treatment twice a day for two weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in brain lesions | Volumetric MRI will be used for calculating changes in the number of lacunar infarctions and the total volume of white matter lesions | 0-24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the cognitive function | Cognitive function will be evaluated by mini-mental state examination (MMSE) and the Montreal Cognitive Assessment (MoCA). | 0-24 months | 
| Changes in the cerebral blood perfusion | Cerebral blood perfusion will be evaluated by Xe-CT. | 0-24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RIPC, remote ischemic preconditioning, random-controlled, double blind