The Effect of RIC on TIA/Stroke in Children With Moyamoya Disease (RIC-PMD-1)

Remote Ischemic Conditioning Prevents Ischemic Cerebrovascular Events In Children With Moyamoya Disease: A Randomized Controlled Trial

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.

Study Overview

• Status: Unknown
• Conditions: Stroke; Children; Moyamoya Disease; TIA
• Intervention / Treatment: Device: RIC group; Device: Sham group

Detailed Description

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
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sijie Li, MD; Phone Number: 1083199439; Email: phoenix0537@sina.com
• Study Contact Backup: Name: Xunming Ji, MD PhD; Phone Number: 108613911077166; Email: Jixunming@vip.163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RIC group; 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.	Device: RIC group; 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 Comparator: sham group; 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.	Device: Sham group; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	during baseline to 12months after therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral perfusion	cerebral perfusion status in the operation side at 12 months posttreatment as assessed by single photon emission computed tomography (SPECT).	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.	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.	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.	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.	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.	changes from baseline to 12months after therapy
The volume 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.	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	during baseline to 12months after therapy
Number of distal radial pulses	professional doctors will check the distal radial pulses	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.	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.	changes from baseline to 6, 12months after therapy
Palpation for tenderness	Professional doctors will definite whether there's a palpation for tenderness	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.	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.	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.	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	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	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	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	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	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	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).	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)	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	from baseline（pre-RIC treatment) to 12 months after therapy

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: 307 Hospital of PLA

Study record dates

Study Major Dates

• Study Start (Anticipated): December 8, 2019
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 19, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Stroke; TIA; pediatric moyamoya disease; Remote ischemic conditioning
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Carotid Artery Diseases; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Stroke; Moyamoya Disease
• Other Study ID Numbers: RIC-PMD-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No