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

Stroke Clinical Trial

— RIC-PMD-1  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03821181
• Other study ID #: RIC-PMD-1
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 8, 2019
• Est. completion date: August 2020

Study information

• Verified date: November 2019
• Source: Capital Medical University
• Contact: Xunming Ji, MD PhD
• Phone: 108613911077166
• Email: Jixunming[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: August 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Children
• Moyamoya Disease
• Stroke
• TIA

Intervention

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 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.

Locations

Country	Name	City	State
China	Xuanwu Hospital, Capital Medical University	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Capital Medical University	307 Hospital of PLA

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of distal radial pulses	professional doctors will check the distal radial pulses	changes from baseline to 6, 12months after therapy
Secondary	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
Secondary	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
Secondary	Palpation for tenderness	Professional doctors will definite whether there's a palpation for tenderness	changes from baseline to 6, 12months after therapy
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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