Safety and Efficacy of RIC in Pediatric Moyamoya Disease Patients Treated With Revascularization Therapy

Not Applicable

• Conditions: Moyamoya Disease; Pediatric

• Registration Number: NCT03546309
• Lead Sponsor: Capital Medical University

Brief Summary

Revascularization surgery has been the standard treatment to prevent ischemic stroke in pediatric Moyamoya disease (MMD) patients with ischemic symptoms. However, perioperative complications, such as hyperperfusion syndrome, new infarct on imaging, or ischemic stroke, are inevitable. Remote ischemic conditioning (RIC) is a noninvasive and easy-to-use neuroprotective strategy, and it has potential effects on preventing hyperperfusion syndrome and ischemic infarction.

Detailed Description

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

Study Timeline

• Study First Submitted: 2018-03-12
• Study First Submitted QC: 2018-06-03
• Study First Posted: 2018-06-06
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-19
• Last Update Posted: 2019-11-20
• Study Start: 2019-12-30
• Primary Completion: 2020-12-30
• Study Completion: 2020-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 68

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
• Suzuki stages concentrated in Stage III and IV
• Presentation with ischemic symptoms, such as transient ischemic attack (TIA), headache, seizure, hemorrhagic stroke, and ischemic stroke confirmed by MRI
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
the incidence of major neurologic complications	during the perioperative period	Including transient ischemic attack, cerebral infarction, intracranial hemorrhage, and seizures.

Secondary Outcome Measures

Name	Time	Method
The score of National Institute of Health stroke scale score	change from baseline (preoperation) at 24 hours, 48 hours, 72 hours, and at 5-7 days or if discharged earlier	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 score of Modified Rankin scale score	change from baseline (pre-RIC treatment) at 180 days after revascularization therapy	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). We 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, at 90 days postoperation. The distribution of mRS will be compared between groups
Symptomatic intracerebral hemorrhage	during the first 180 days after revascularization therapy	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.
Incidence of new infarct in brain	during 72 hours and 180 days after revascularization therapy	Head MRI is a precise method which is commonly used to evaluate weather there's new infarct in brain.
Visual inspection for local edema	within 7days after RIC treatment	Professional oculists will check the fundus oculi to evaluate whether there is local edema.
Angiographic outcome	180 days after revascularization therapy	Angiographic outcome will be assessed following Matsushima's criteria (proportion of the middle cerebral artery territory with revascularization from collaterals from the external carotid artery through the burr holes): Grade A: \>2/3; Grade B: between 1/3 and 2/3; Grade C: \<1/3.
Death and adverse event	180 days after revascularization therapy	All causes of death will be included to compute mortality at 180 days postoperation, and mortality will be compared between groups. Any adverse event will be reported and its relationship with the RIC intervention will be evaluated.
Infarct volume in brain	during 72 hours and 180 days after revascularization therapy	Head MRI is a precise method which is commonly used to evaluate infarct size.
Distal radial pulses	within 7 days after RIC treatment	professional doctors will check the distal radial pulses
The number of patients with erythema,and/or skin lesions related to RIC	within 7days after RIC treatment	Professional doctors will check it and the investigator will record the number.
Palpation for tenderness	within 7days after RIC treatment	Professional doctors will check it.
The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure	within 7days after RIC treatment	The investigator will record the number.
The number of patients with any other adverse events related to RIC intervention	within 7days after RIC treatment	The investigator will record the number.
The score of ABCD2	change from baseline (pre-RIC treatment) at 180 days after revascularization therapy	We 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
The level of S-100A4	change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months postoperation	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
The level of matrix metalloproteinase 9 (MMP-9)	change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation	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
The level of basic fibroblast growth factor	change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation	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
The level of platelet derived growth factor	change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation	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
The level of vascular endothelial growth factor	change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation	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
the score of PSQI	0-30 days	The Pittsburgh Sleep Quality Index (PSQI) is a standardized questionnaire used to assess sleep quality and disturbances over a one-month time interval.
the score of SNAP-IV	0-30 days	SNAP-IV (Swanson, Nolan, and Pelham Teacher and Parent Rating Scale) is a widely used assessment tool designed to evaluate behavioral and emotional problems in children and adolescents.
cerebral perfusion status	0-3 months	cerebral perfusion status in the operation side at 3 months posttreatment as assessed by magnetic resonance perfusion

Trial Locations

Locations (1)

The Fifth Medical Center of Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China