The Safety and Efficacy of RIC on Adult Moyamoya Disease

Study Overview
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Brief Summary
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There are a series of symptoms such as ischemic stroke、transient ischemic attack 、hemorrhagic stroke、headache 、seizure and so on in moyamoya disease( MMD) patients .Nowadays, revascularization is the only effective way for ischemic MMD and there is no effective conservative treatment for MMD. This study was to explore the safety and efficacy of remote ischemic conditioning(RIC ) on adult MMD patients.

Detailed Description
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There are a series of symptoms such as ischemic stroke、transient ischemic attack 、hemorrhagic stroke、headache 、seizure and so on in moyamoya disease. Nowadays, revascularization is the only effective way for ischemic MMD while controversial for hemorrhagic MMD patients. Surgical complications including hyperperfusion syndrome, cerebral infarction or bleeding often occurred postoperatively. There is no effective conservative treatment for MMD up to now. Remote ischemic conditioning is Remote ischemic conditioning (RIC) is a noninvasive and easy-to-use neuroprotective strategy, and it has potential effects on preventing ischemia reperfusion injury and ischemic infarction.This study was to explore the safety and efficacy of remote ischemic conditioning on adult MMD patients.

Official Title
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The Safety and Effect of Remote Ischemic Conditioning on Adult Moyamoya Disease

Conditions
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Moyamoya Disease

Intervention / Treatment
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* Device: RIC
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-60 years All of the patients underwent digital subtraction angiography (DSA) and met the current diagnostic criteria recommended by the Research Committee on MMD of the Ministry of Health and Welfare of Japan in 2012. mRs≤3 Informed consent obtained from patient or acceptable patient's surrogate. Exclusion Criteria: Patients with acute ischemic or hemorrhagic stroke within 3 months. Severe hepatic or renal dysfunction. Severe hemostatic disorder or severe coagulation dysfunction. Severe cardiac diseases. Patients with severe existing neurological or psychiatric disease Patients with moyamoya syndrome caused by autoimmune disease, Down syndrome , neurofibromatosis, leptospiral infection, or previous skull-base radiation therapy. Patients have been done or plan to accept revascularization surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: RIC group<br>Patients allocated to the RIC group will undergo RIC procedure during which bilateral arm cuffs are inflated to a pressure of 50 mmHg over systolic blood pressure for five cycles of 5 min followed by 5 min of relaxation of the cuffs. They will also accept medication treatment by professional neurologists. | Device: RIC<br>* Patients allocated to the RIC group will undergo RIC procedure during which bilateral arm cuffs are inflated to a pressure of 50 mmHg over systolic blood pressure for five cycles of 5 min followed by 5 min of relaxation of the cuffs.<br>|
| Other: Medication group<br>Patients allocated to Medication group will accept medication treatment by professional neurologists. | Drug: Aspirin<br>* patients will accept medication guided by neurologists<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement ratio of mean cerebral blood flow | Cerebral blood flow refers to the flow of blood through a certain cross-sectional area of cerebrovascular in a unit time. Patients' CBF will be detected by arterial spin labeling. In each hemisphere, middle cerebral artery territory was divided into ten regions according to Albert Stroke Program Early CT score (ASPECTS), regions of interest (ROI) were drawn manually in each of territory of MCA to determine the absolute CBF values. improvement ratio of mean CBF= mCBF atter treatment-mCBF baseline/mCBF baseline. | change from the baseline to12 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of ischemic stroke | ischemic stroke is diagnosed by symptoms of neurologic deficit or head CT and MRI. | from the baseline to 12 months after treatment | 
| incidence of transient ischemic attack | TIA is diagnosed by patients' transient neurologic deficit | from the baseline to 12 months after treatment | 
| incidence of hemorrhagic stroke | hemorrhagic stroke is diagnosed by head CT | from the baseline to 12 months after treatment | 
| The level of matrix metalloproteinase 9 (MMP-9) | Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation | change from the baseline to 3, 6, 12 months after treatment | 
| The level of vascular endothelial growth factor | Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation | change from the baseline to 3, 6, 12 months after treatment | 
| The level of basic fibroblast growth factor | Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation | change from the baseline to 3, 6 ,12 months after treatment | 
| The rate of death and adverse event | All causes of death will be included to compute mortality at 12 months after therapy | change from the baseline to 12 months after treatment | 
| The number of patients with erythema,and/or skin lesions related to RIC | Professional doctors will check it and the investigator will record the number. | change from the baseline to 12 months after treatment | 
| The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure | the investigator will record the number. | change from the baseline to 12 months after treatment | 
| The rate of progression of stenosis or occlusion at Willis circle | Progression of stenosis or occlusion at Willis circle was evaluated by TOF-MRA, which was defined as the the stenosis or occlusion was progressed to another part of Willis circle, like stenosis progressed from M1 to M2-M4 et al, or in the same part, stenosis progressed to occlusion. | 12 months after therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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moyamoya disease, remote ischemic conditioning, cerebral blood flow