Back to resultsThe Effect of RIC on TIA/Stroke in Children With Moyamoya Disease (RIC-PMD-1)
Primary Purpose
Moyamoya Disease, TIA, Children
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
RIC group
Sham group
Sponsored by
About this trial
This is an interventional prevention trial for Moyamoya Disease focused on measuring pediatric moyamoya disease, TIA, Stroke, Remote ischemic conditioning
Eligibility Criteria
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.
Sites / Locations
- Xuanwu Hospital, Capital Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
RIC group
sham group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Cerebral perfusion
cerebral perfusion status in the operation side at 12 months posttreatment as assessed by single photon emission computed tomography (SPECT).
The mean blood flow velocity of cerebral vascular detected by TCCD
TCCD means tran-scranial color-coded duplex sonography.
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.
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.
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.
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.
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.
The rate of death and adverse event
All causes of death will be included to compute mortality at 12 months after therapy
Number of distal radial pulses
professional doctors will check the distal radial pulses
Visual inspection of local edema of fundus oculi
Professional oculists will visually inspect the fundus oculi to evaluate whether there is local edema.
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.
Palpation for tenderness
Professional doctors will definite whether there's a palpation for tenderness
The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure
The investigator will record the number.
The number of patients with any other adverse events related to RIC intervention
The investigator will record the number.
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.
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
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
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
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
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
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
cerebral perfusion examined by SPECT
cerebral perfusion status post-treatment will be assessed by single photon emission computed tomography (SPECT).
cerebral perfusion examined by ASL
cerebral perfusion status post-treatment will be assessed by arterial spin labeling(ASL)
variant of the RNF-213 gene
The investigators will save the blood sample in -20℃，and detect the variant RNF-213 gene
Full Information
NCT ID
NCT03821181
First Posted
January 22, 2019
Last Updated
November 19, 2019
Sponsor
Capital Medical University
Collaborators
307 Hospital of PLA
1. Study Identification
Unique Protocol Identification Number
NCT03821181
Brief Title
The Effect of RIC on TIA/Stroke in Children With Moyamoya Disease
Acronym
RIC-PMD-1
Official Title
Remote Ischemic Conditioning Prevents Ischemic Cerebrovascular Events In Children With Moyamoya Disease: A Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 8, 2019 (Anticipated)
Primary Completion Date
July 2020 (Anticipated)
Study Completion Date
August 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Capital Medical University
Collaborators
307 Hospital of PLA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Moyamoya Disease, TIA, Children, Stroke
Keywords
pediatric moyamoya disease, TIA, Stroke, Remote ischemic conditioning
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RIC group
Arm Type
Experimental
Arm Description
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.
Arm Title
sham group
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
RIC group
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham group
Intervention Description
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.
Primary Outcome Measure Information:
Title
The incidence rate of transient ischemic attack(TIA)
Description
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
Title
The incidence rate of ischemic stroke
Description
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 Outcome Measure Information:
Title
Cerebral perfusion
Description
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
Title
The mean blood flow velocity of cerebral vascular detected by TCCD
Description
TCCD means tran-scranial color-coded duplex sonography.
Time Frame
changes form baseline to 6months，12months after therapy
Title
The score of National Institute of Health stroke scale score
Description
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.
Time Frame
during baseline to 12months after therapy
Title
The score of Modified Rankin scale score
Description
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
Title
Incidence rate of symptomatic intracerebral hemorrhage
Description
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
Title
The number of cerebral lacunar infarction
Description
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
Title
The volume of cerebral lacunar infarction
Description
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 12 months after therapy
Title
The rate of death and adverse event
Description
All causes of death will be included to compute mortality at 12 months after therapy
Time Frame
during baseline to 12months after therapy
Title
Number of distal radial pulses
Description
professional doctors will check the distal radial pulses
Time Frame
changes from baseline to 6, 12months after therapy
Title
Visual inspection of local edema of fundus oculi
Description
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
Title
The number of patients with erythema,and/or skin lesions related to RIC
Description
Professional doctors will check it and the investigator will record the number.
Time Frame
changes from baseline to 6, 12months after therapy
Title
Palpation for tenderness
Description
Professional doctors will definite whether there's a palpation for tenderness
Time Frame
changes from baseline to 6, 12months after therapy
Title
The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure
Description
The investigator will record the number.
Time Frame
during baseline to 12months after therapy
Title
The number of patients with any other adverse events related to RIC intervention
Description
The investigator will record the number.
Time Frame
during baseline to 12months after therapy
Title
The score of ABCD2
Description
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
Title
The level of S-100A4
Description
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
Title
The level of matrix metalloproteinase 9 (MMP-9)
Description
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
Title
The level of basic fibroblast growth factor
Description
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
Title
The level of platelet derived growth factor
Description
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
Title
The level of vascular endothelial growth factor
Description
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
Title
The level of hs-CRP(high-sensitive C-reactive protein)
Description
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
Title
cerebral perfusion examined by SPECT
Description
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
Title
cerebral perfusion examined by ASL
Description
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
Title
variant of the RNF-213 gene
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xunming Ji, MD PhD
Phone
108613911077166
Email
Jixunming@vip.163.com;
First Name & Middle Initial & Last Name or Official Title & Degree
Sijie Li, MD
Phone
1083199439
Email
phoenix0537@sina.com
Facility Information:
Facility Name
Xuanwu Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100053
Country
China
12. IPD Sharing Statement
Learn more about this trial
The Effect of RIC on TIA/Stroke in Children With Moyamoya Disease
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