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

November 19, 2019 updated by: Ji Xunming,MD,PhD, Capital Medical University

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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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.
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.
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)
Time Frame: during baseline to 12months after therapy
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
Time Frame: during baseline to 12months after therapy
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
Time Frame: change from baseline to 12months after therapy
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
Time Frame: changes form baseline to 6months,12months after therapy
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
Time Frame: during baseline to 12months after therapy
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
Time Frame: during baseline to 12months after 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). 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
Time Frame: during baseline to 12months after 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.
during baseline to 12months after therapy
The number of cerebral lacunar infarction
Time Frame: changes from baseline to 12months after therapy
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
Time Frame: changes from baseline to 12 months after therapy
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
Time Frame: during baseline to 12months after therapy
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
Time Frame: changes from baseline to 6, 12months after therapy
professional doctors will check the distal radial pulses
changes from baseline to 6, 12months after therapy
Visual inspection of local edema of fundus oculi
Time Frame: changes from baseline to 6, 12months after therapy
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
Time Frame: changes from baseline to 6, 12months after therapy
Professional doctors will check it and the investigator will record the number.
changes from baseline to 6, 12months after therapy
Palpation for tenderness
Time Frame: changes from baseline to 6, 12months after therapy
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
Time Frame: during baseline to 12months after therapy
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
Time Frame: during baseline to 12months after therapy
The investigator will record the number.
during baseline to 12months after therapy
The score of ABCD2
Time Frame: during baseline to 12months after therapy
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
Time Frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy
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)
Time Frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy
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
Time Frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy
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
Time Frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy
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
Time Frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy
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)
Time Frame: change from baseline (pre-RIC treatment) to 6 months ,12 months after therapy
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
Time Frame: from baseline(pre-RIC treatment) to 12 months after therapy
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
Time Frame: from baseline(pre-RIC treatment) to 12 months after therapy
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
Time Frame: from baseline(pre-RIC treatment) to 12 months after therapy
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

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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