Back to resultsSafety and Efficacy of RIC in Pediatric Moyamoya Disease Patients Treated With Revascularization Therapy (RIC-PMD)
Primary Purpose
Moyamoya Disease, Pediatric
Status
Unknown status
Phase
Not Applicable
Locations
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, remote ischemic conditioning, revascularization therapy
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
- 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.
Sites / Locations
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
cerebral perfusion cerebral perfusion
cerebral perfusion status in the operation side at 6 months posttreatment as assessed by single photon emission computed tomography (SPECT).
Secondary Outcome Measures
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 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). 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
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
Head MRI is a precise method which is commonly used to evaluate weather there's new infarct in brain.
Angiographic outcome
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
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
Head MRI is a precise method which is commonly used to evaluate infarct size.
Distal radial pulses
professional doctors will check the distal radial pulses
Visual inspection for local edema
Professional oculists will check 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 check it.
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
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
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
Full Information
NCT ID
NCT03546309
First Posted
March 12, 2018
Last Updated
November 19, 2019
Sponsor
Capital Medical University
1. Study Identification
Unique Protocol Identification Number
NCT03546309
Brief Title
Safety and Efficacy of RIC in Pediatric Moyamoya Disease Patients Treated With Revascularization Therapy
Acronym
RIC-PMD
Official Title
Safety and Efficacy of Remote Ischemic Conditioning in Pediatric Moyamoya Disease Patients Treated With Revascularization Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 30, 2019 (Anticipated)
Primary Completion Date
December 30, 2020 (Anticipated)
Study Completion Date
December 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Capital Medical University
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Moyamoya Disease, Pediatric
Keywords
pediatric moyamoya disease, remote ischemic conditioning, revascularization therapy
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
68 (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
cerebral perfusion cerebral perfusion
Description
cerebral perfusion status in the operation side at 6 months posttreatment as assessed by single photon emission computed tomography (SPECT).
Time Frame
change from baseline（pre-RIC treatment) at 180 days after revascularization therapy
Secondary Outcome Measure Information:
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.
Time Frame
change from baseline (preoperation) at 24 hours, 48 hours, 72 hours, and at 5-7 days or if discharged earlier
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). 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
Time Frame
change from baseline (pre-RIC treatment) at 180 days after revascularization therapy
Title
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 the first 180 days after revascularization therapy
Title
Incidence of new infarct in brain
Description
Head MRI is a precise method which is commonly used to evaluate weather there's new infarct in brain.
Time Frame
during 72 hours and 180 days after revascularization therapy
Title
Angiographic outcome
Description
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.
Time Frame
180 days after revascularization therapy
Title
Death and adverse event
Description
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.
Time Frame
180 days after revascularization therapy
Title
Infarct volume in brain
Description
Head MRI is a precise method which is commonly used to evaluate infarct size.
Time Frame
during 72 hours and 180 days after revascularization therapy
Title
Distal radial pulses
Description
professional doctors will check the distal radial pulses
Time Frame
within 7 days after RIC treatment
Title
Visual inspection for local edema
Description
Professional oculists will check the fundus oculi to evaluate whether there is local edema.
Time Frame
within 7days after RIC treatment
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
within 7days after RIC treatment
Title
Palpation for tenderness
Description
Professional doctors will check it.
Time Frame
within 7days after RIC treatment
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
within 7days after RIC treatment
Title
The number of patients with any other adverse events related to RIC intervention
Description
The investigator will record the number.
Time Frame
within 7days after RIC treatment
Title
The score of ABCD2
Description
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
Time Frame
change from baseline (pre-RIC treatment) at 180 days after revascularization 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) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months postoperation
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) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
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) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
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) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
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) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
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
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xunming Ji, MD PhD
Phone
108613911077166
Email
807595234@qq.com;
First Name & Middle Initial & Last Name or Official Title & Degree
Sijie Li, MD
Phone
1083199439
Email
phoenix0537@sina.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
18048855
Citation
Kuriyama S, Kusaka Y, Fujimura M, Wakai K, Tamakoshi A, Hashimoto S, Tsuji I, Inaba Y, Yoshimoto T. Prevalence and clinicoepidemiological features of moyamoya disease in Japan: findings from a nationwide epidemiological survey. Stroke. 2008 Jan;39(1):42-7. doi: 10.1161/STROKEAHA.107.490714. Epub 2007 Nov 29.
Results Reference
background
PubMed Identifier
15046649
Citation
Kim SK, Seol HJ, Cho BK, Hwang YS, Lee DS, Wang KC. Moyamoya disease among young patients: its aggressive clinical course and the role of active surgical treatment. Neurosurgery. 2004 Apr;54(4):840-4; discussion 844-6. doi: 10.1227/01.neu.0000114140.41509.14.
Results Reference
background
PubMed Identifier
18483458
Citation
Kim JE, Oh CW, Kwon OK, Park SQ, Kim SE, Kim YK. Transient hyperperfusion after superficial temporal artery/middle cerebral artery bypass surgery as a possible cause of postoperative transient neurological deterioration. Cerebrovasc Dis. 2008;25(6):580-6. doi: 10.1159/000132205. Epub 2008 May 16.
Results Reference
background
PubMed Identifier
21221039
Citation
Fujimura M, Shimizu H, Inoue T, Mugikura S, Saito A, Tominaga T. Significance of focal cerebral hyperperfusion as a cause of transient neurologic deterioration after extracranial-intracranial bypass for moyamoya disease: comparative study with non-moyamoya patients using N-isopropyl-p-[(123)I]iodoamphetamine single-photon emission computed tomography. Neurosurgery. 2011 Apr;68(4):957-64; discussion 964-5. doi: 10.1227/NEU.0b013e318208f1da.
Results Reference
background
PubMed Identifier
25423271
Citation
Funaki T, Takahashi JC, Takagi Y, Kikuchi T, Yoshida K, Mitsuhara T, Kataoka H, Okada T, Fushimi Y, Miyamoto S. Unstable moyamoya disease: clinical features and impact on perioperative ischemic complications. J Neurosurg. 2015 Feb;122(2):400-7. doi: 10.3171/2014.10.JNS14231. Epub 2014 Nov 28.
Results Reference
background
PubMed Identifier
28174194
Citation
Zhao W, Meng R, Ma C, Hou B, Jiao L, Zhu F, Wu W, Shi J, Duan Y, Zhang R, Zhang J, Sun Y, Zhang H, Ling F, Wang Y, Feng W, Ding Y, Ovbiagele B, Ji X. Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial. Circulation. 2017 Apr 4;135(14):1325-1335. doi: 10.1161/CIRCULATIONAHA.116.024807. Epub 2017 Feb 7.
Results Reference
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Safety and Efficacy of RIC in Pediatric Moyamoya Disease Patients Treated With Revascularization Therapy
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