The Effect of RIC on TIA/Stroke in Children With Moyamoya Disease

Capital Medical University50 enrolled

Overview

Moyamoya disease is a common reason of transient ischemic attack (TIA) and stroke in children. Remote ischemic conditioning (RIC) has been shown to prevent recurrent stroke in intracranial arterial stenosis, but it is unclear whether RIC can prevent TIA or stroke in children with moyamoya disease. This study aims to evaluate the effect of RIC on TIA/stroke in children with moyamoya disease.

This study will provide insights into the preliminary proof of principle, safety, and efficacy of RIC in pediatric MMD patients, and this data will provide parameters for future larger scale clinical trials if efficacious

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Moyamoya Disease TIA Children Stroke

Interventions

RIC groupDEVICE

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.

Sham groupDEVICE

patients allocated to the sham group will undergo a sham RIC procedure during which bilateral arm cuffs are inflated to a pressure of 30 mmHg for five cycles of 5 min, followed by 5 min of relaxation of the cuffs.

Eligibility

Sex: ALLMin age: 1 MonthMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age: ≥0 and ≤18 * all of the patients underwent digital subtraction angiography and met the current diagnostic criteria recommended by the Research Committee on MMD (Spontaneous Occlusion of the Circle of Willis) of the Ministry of Health and Welfare of Japan in 2012 * The CVR of patients detected by SPECT is not impaired severely * The patients didn't suffer stroke before. * Informed consent obtained from patient or acceptable patient's surrogate Exclusion Criteria: * Severe hepatic or renal dysfunction * Severe hemostatic disorder or severe coagulation dysfunction * Patients with unilateral MMD or the presence of secondary moyamoya phenomenon caused by autoimmune disease, Down syndrome, neurofibromatosis, leptospiral infection, or previous skull-base radiation therapy * Any of the following cardiac disease - rheumatic mitral and or aortic stenosis, prosthetic heart valves, atrial fibrillation, atrial flutter, sick sinus syndrome, left atrial myxoma, patent foramen ovale, left ventricular mural thrombus or valvular vegetation, congestive heart failure, bacterial endocarditis, or any other cardiovascular condition interfering with participation * Serious, advanced, or terminal illnesses with anticipated life expectancy of less than one year * Patient participating in a study involving other drug or device trial study * Patients with existing neurological or psychiatric disease that would confound the neurological or functional evaluations * Unlikely to be available for follow-up for 3 months * Contraindication for RIC - severe soft-tissue injury, fracture, or peripheral vascular disease in the upper limbs.

Locations (1)

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

The incidence rate of transient ischemic attack(TIA)

TIA means transient ischemic attack, two neurologists will evaluate patients with ischemic symptoms and make diagnosis.magnetic reasoning imaging (MRI) scan will be performed to confirm intracerebral hemorrhage, and the imaging will be evaluated by two independent neuroradiologists who are blinded to the study assignment.

Time frame: during baseline to 12months after therapy

The incidence rate of ischemic stroke

Two neurologists will evaluate patients with ischemic symptoms and make diagnosis.magnetic reasoning imaging (MRI) scan will be performed to confirm intracerebral hemorrhage, and the imaging will be evaluated by two independent neuroradiologists who are blinded to the study assignment.

Time frame: during baseline to 12months after therapy

Secondary Outcomes

Cerebral perfusion

cerebral perfusion status in the operation side at 12 months posttreatment as assessed by single photon emission computed tomography (SPECT).

Time frame: change from baseline to 12months after therapy

The mean blood flow velocity of cerebral vascular detected by TCCD

TCCD means tran-scranial color-coded duplex sonography.

Time frame: changes form baseline to 6months，12months after therapy

The score of National Institute of Health stroke scale score

National Institute of Health Stroke Scale (NIHSS) is considered as a standardized assessment of neurological functions in the acute phase of stroke, and it is generally used to quantify patient's neurological impairments on 15 items in 11 fields of different neurological status.The score of the scale ranges from 0 to 42.And higher score indicates worse neurological function.The NHISS will be assessed by certified study investigator, who is blinded to the treatment assignment.

Central Contacts

Xunming Ji, MD PhD

CONTACT

108613911077166 Jixunming@vip.163.com;

Sijie Li, MD

CONTACT

1083199439 phoenix0537@sina.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: during baseline to 12months after therapy

The score of Modified Rankin scale score

The Modified Rankin Scale Score (mRS) is the most comprehensive and most widely used primary outcome measurement to assess the neurological functional disability in contemporary acute stroke trials. The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranges from 0 (no symptom) to 5 (severe disability) and 6 (death). The investigators will use mRS to evaluate the degree of disability or dependence during daily activities. The mRS will be assessed by certified study investigator, who is blinded to the treatment assignment.

Time frame: during baseline to 12months after therapy

Incidence rate of symptomatic intracerebral hemorrhage

Symptomatic intracranial hemorrhage, including any subarachnoid hemorrhage associated with clinical symptoms and symptomatic intracerebral hemorrhage. Head computed tomography or magnetic reasoning imaging (MRI) scan will be performed to confirm intracerebral hemorrhage, and the imaging will be evaluated by two independent neuroradiologists who are blinded to the study assignment.

Time frame: during baseline to 12months after therapy

The number of cerebral lacunar infarction

magnetic reasoning imaging (MRI) scan will be performed to confirm intracerebral hemorrhage, and the imaging will be evaluated by two independent neuroradiologists who are blinded to the study assignment.

Time frame: changes from baseline to 12months after therapy

The volume of cerebral lacunar infarction

Time frame: changes from baseline to 12 months after therapy

The rate of death and adverse event

All causes of death will be included to compute mortality at 12 months after therapy

Time frame: during baseline to 12months after therapy

Number of distal radial pulses

professional doctors will check the distal radial pulses

Time frame: changes from baseline to 6, 12months after therapy

Visual inspection of local edema of fundus oculi

Professional oculists will visually inspect the fundus oculi to evaluate whether there is local edema.

Time frame: changes from baseline to 6, 12months after therapy

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.

Time frame: changes from baseline to 6, 12months after therapy

Palpation for tenderness

Professional doctors will definite whether there's a palpation for tenderness

Time frame: changes from baseline to 6, 12months after therapy

The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure

The investigator will record the number.

Time frame: during baseline to 12months after therapy

The number of patients with any other adverse events related to RIC intervention

The investigator will record the number.

Time frame: during baseline to 12months after therapy

The score of ABCD2

When subjects are diagnosed as TIA within 12 months after therapy ,The investigators use this scale to evaluate the patients' risk of stroke who with TIA .The score of the scale ranges from 0 to 7, and the higher score indicates higher risk of stroke in the patients who with TIA.The scale will be assessed by qualified investigator who are blinded to the treatment assignment.

Time frame: during baseline to 12months after therapy

The level of S-100A4

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

Time frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy

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

Time frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy

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

Time frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy

The level of platelet derived 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

Time frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy

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

Time frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy

The level of hs-CRP(high-sensitive C-reactive protein)

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

Time frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy

cerebral perfusion examined by SPECT

cerebral perfusion status post-treatment will be assessed by single photon emission computed tomography (SPECT).

Time frame: from baseline（pre-RIC treatment) to 12 months after therapy

cerebral perfusion examined by ASL

cerebral perfusion status post-treatment will be assessed by arterial spin labeling(ASL)

Time frame: from baseline（pre-RIC treatment) to 12 months after therapy

variant of the RNF-213 gene

The investigators will save the blood sample in -20℃，and detect the variant RNF-213 gene

Time frame: from baseline（pre-RIC treatment) to 12 months after therapy