The Efficacy of Remote Ischemic Conditioning on Stroke-induced Immunodeficiency

Study Overview
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Brief Summary
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to detect the effects of RIC on stroke-induced immunodeficiency and inflammation response in acute ischemic stroke patients

Detailed Description
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Remote ischemic conditioning, consisting of several brief cycles of intermittent ischemia-reperfusion of the arm or leg, may potentially confer systemic protection against prolonged ischemia in a distant organ. Numerous reports have confirmed its strongest endogenous neuroprotection against brain injury after stroke, of which the immune mechanisms are majorly involved in RIC. At the same time, the inflammation response plays a great role in stroke development, which may expand the infarct area. Stroke-induced immunodeficiency can potentiate stroke-associated pneumonia, which is an important cause of death after strokes. In this study, the investigators will assess the effect of RIC on stroke-induced immunodeficiency and inflammation response in AIS patients.

Official Title
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The Efficacy of Remote Ischemic Conditioning on Stroke-induced Immunodeficiency

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Device: remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 years old; Confirmed diagnosis of acute ischemic stroke(AIS) with onset of symptoms within 48h at recruitment; NIHSS score: ≤15; Prestroke modified Rankin Scale(mRS) ≤2; subject or his or her legally authorized representative was able to provide informed consent. Exclusion Criteria: uncontrolled hypertension (defined as systolic blood pressure ≥200 mmHg); participation in another device or drug trial simultaneously; any vascular, soft tissue, or orthopedic injury (eg, superficial wounds and fractures of the arm) that contraindicated unilateral arm ischemic preconditioning; peripheral vascular disease (especially subclavian arterial and upper limb artery stenosis or occlusion); Women who have a positive pregnancy test; History of malignancies; Using remote ischemic conditioning within the preceding 1 week; known infection at admission; a history of infection or the use of antibiotics, immunosuppressants, or steroids within the preceding 3 months. Other conditions are not suitable for this trial (evaluated by researchers)

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AIS-RIC<br>RIC is a physical strategy performed through cuffs placed on the unilateral arm and inflated to 180 mmHg for 5-min followed by deflation for 5-min, the procedures are performed repeatedly for 5 times. This group of patients received regular therapy of acute ischemic stroke plus unilateral arm of RIC intervention. | Device: remote ischemic conditioning<br>* RIC is a physical strategy performed by an electric device with cuffs placed on the unilateral arm and inflated to 180 mmHg for 5-min followed by deflation for 5-min, the procedures are performed repeatedly for 5 times.<br>|
| No Intervention: AIS<br>This group of patients received regular therapy of acute ischemic stroke. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of mHLA-DR level in plasma | through flow cytometry | change from baseline to 2(±24h)days, and at 7(±24h)days after admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of TLR-2, TLR-4 level in plasma | through flow cytometry | change from baseline to 2(±24h)days, and at 7(±24h)days after admission | 
| Incidence of Stroke-associated Pneumonia within 1 week | Stroke-associated Pneumonia diagnostic criteria base on the consensus of 2015 Stroke-associated Pneumonia diagnostic criteria base on the consensus of 2015 Stroke-associated Pneumonia diagnostic criteria base on the consensus of 2015 | within 7(±24h)days after admission | 
| Number of Participants with physician-diagnosed pneumonia within 90 days after stroke onset | Number of Participants with Physician-diagnosed Pneumonia within 90 days after stroke onset Physician-diagnosed Pneumonia within 90 days | 90( ±7days) days after ischemic stroke onset | 
| White blood cell count, monocyte count | through routine blood test | baseline, 2(±24h) days, 7(±24h) days after admission | 
| Concentration of IL-1β、IL-6、IL-10、TNFα（CRP if patients are infected）level | inflammatory cytokines | baseline, 2(±24h)days, and at 7(±24h)days after admission | 
| Number of Participants with Favorable outcome at 90 days | definition of favorable outcome: mRS : 0-2 or NIHSS: 0-1 | 90 days after ischemic stroke onset | 
| Number of Participants with any adverse events | adverse events include stroke extension, gastrointestinal bleed, cardiac events, increased liver or renal enzymes, and transfer to intensive care unit. | during baseline to 90 days after stroke onset | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, Remote ischemic preconditioning, Stroke-induced immunodeficiency, Stroke-associated Pneumonia, inflammation response