Effects of Remote Ischemic Pre-Conditioning in Moyamoya Disease Patients

Study Overview
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Brief Summary
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In the present study, investigators evaluated whether RIPC reduce the major neurological complications in adult moyamoya disease patients undergoing encephaloduroarteriosynangiosis (EDAS).

Detailed Description
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BACKGROUND: Brain ischemia and injury contributed to perioperative morbidity and mortality in revascularization surgery. Remote ischemic preconditioning (RIPC), brief periods of ischemia followed by reperfusion, can provide systemic protection for prolonged ischemia. Previous study found combined remote ischemic pre- and post-conditioning can be effective in reducing neurologic complications and the duration of hospitalization in moyamoya patients undergoing direct revascularization.In order to investigate whether RIPC before EDAS can protect these patients from the perioperative and long-term complications, a prospective randomized controlled trial will be performed in the current study. DESIGNING: About 328 patients who are eligible for carotid artery stenting will be randomly assigned in 1:1 ratio to RIPC group and sham RIPC group (control). Remote limb ischemic preconditioning (RIPC) is consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, it is induced by a sphygmomanometer placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min, patients in the RIPC group will do it twice a day for at least five days before EDAS. Patients in the sham RIPC group receive sham RIPC treatment, which is consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, induced by a sphygmomanometer placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min, they will do it twice a day for at least five days before EDAS. Cerebral injury is assessed by plasma Human Soluble protein-100B (S-100B) and Neuron specific enolase (NSE). Clinical outcomes are determined by cerebrovascular events (including ischemic stroke, transient ischemic attack (TIA), cerebral hemorrhage and transient neurological deficit) and death or dependent.

Official Title
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Effects of Remote Ischemic Pre-Conditioning on Neurologic Complications in Adult Ischemic Moyamoya Disease Patients Undergoing Encephaloduroarteriosynangiosis

Conditions
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Moyamoya Disease, Remote Ischemic Preconditioning

Intervention / Treatment
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* Procedure: Remote ischemic preconditioning
* Procedure: Sham remote ischemic preconditioning
* Procedure: Encephaloduroarteriosynangiosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who diagnosed with moyamoya disease Adults 18 to 65 years of age The onset symptoms manifested as ischemic symptoms (TIA or stroke) or atypical symptoms (headache, epilepsy or asymptomatic) Able to receive the necessary imaging examination Patients who pre-agreed to the study Exclusion Criteria: Prior cerebral hemorrhage history Other brain or cerebrovascular disease Previous history of revascularization surgery Dependent (mRS > 2) Receive other type of revascularization surgery Peripheral blood vessel disease (especially subclavian arterial and upper limb artery stenosis or occlusion). Patients who do not agree with the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham RIPC group<br>Treatment:Patients in this group received standard medical therapy and sham remote ischemic preconditioning treatment. Device:Sham RIPC consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by a sphygmomanometer placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min, each patient in Sham RIPC group do it twice a day for at least five days before encephaloduroarteriosynangiosis. Procedure: Encephaloduroarteriosynangiosis | Procedure: Sham remote ischemic preconditioning<br>* Sham remote ischemic preconditioning consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by a sphygmomanometer placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min.<br>* Other names: Sham RIPC;Procedure: Encephaloduroarteriosynangiosis<br>* Encephaloduroarteriosynangiosis is an indirect revascularization surgery of moyamoya disease<br>* Other names: EDAS;|
| Experimental: RIPC group<br>Treatment:Patients in this group received standard medical therapy and remote ischemic preconditioning (RIPC) treatment. Device:RIPC consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by a sphygmomanometer placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min,each patient in the RIPC group do it twice a day for at least five days before encephaloduroarteriosynangiosis. Procedure: Encephaloduroarteriosynangiosis | Procedure: Remote ischemic preconditioning<br>* Remote ischemic preconditioning consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by a sphygmomanometer placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min.<br>* Other names: RIPC;Procedure: Encephaloduroarteriosynangiosis<br>* Encephaloduroarteriosynangiosis is an indirect revascularization surgery of moyamoya disease<br>* Other names: EDAS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Cerebrovascular Events. | Cerebrovascular events included ischemic stroke, transient ischemic attack (TIA), cerebral hemorrhage and hyperperfusion syndrome. | postoperative one month | 
| Number of Patients Dependent or Death | Dependent included the modified Rankin Scale (mRS) > 2. Death included any reason caused death. | postoperative one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Severity of the Ischemic Stroke after Surgery | The severity of the ischemic stroke was evaluated by the white matter hyperintensities volume on the MRI, the neurological deficits duration and the Modified Rankin Scale (mRS) of patients. | postoperative one month | 
| Number of Patients Occured Re-stroke at Follow-up Period | Re-stroke included ischemic stroke and hemorrhagic stroke. | 6 months and 12 months after EDAS | 
| Number of Patients Dependent or Death at Follow-up Period | Dependent included the modified Rankin Scale (mRS) > 2. Death included any reason caused death. | 6 months and 12 months after EDAS | 
| Number of Patients with Improved Neurological Function at Follow-up Period | The modified Rankin Scale (mRS) decreased at the follow-up period compared to preoperative scores | 6 months and 12 months after EDAS | 
| Perfusion Status of Patients at Follow-up Period | The perfusion status detected by stages of pre-infarction period based on computed tomography perfusion imaging | 6 months and 12 months after EDAS | 
| Number of Patients With Any Side Effects of Remote Ischemic Preconditioning (RIPC) Treatment. | The side effects referred to any side effects of RIPC or sham RIPC treatment, not including the sides effect of medications and EDAS. | From baseline to 12 months after treatment | 
| Participants Who Got New Diffusion-weighted Imaging (DWI) Lesions on Post-treatment Magnetic Resonance Imaging (MRI) Scans. | The presence of ≥1 new brain lesions on DWI | Within 48 hours after EDAS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moyamoya Disease, Cerebrovascular Disorders, Arterial Occlusive Diseases, Ischemia