Back to resultsSafety and Efficacy of Remote Ischemic Conditioning Combined EDAS on Ischemic Moyamoya Disease (RIC-IMD)
Primary Purpose
Moyamoya Disease
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
RIC plus EDAS
EDAS
Sponsored by
About this trial
This is an interventional treatment trial for Moyamoya Disease focused on measuring moyamoya disease, EDAS, remote ischemic conditioning, cerebral blood flow
Eligibility Criteria
Inclusion Criteria:
- Subjects who were diagnosed as moyamoya disease by the diagnostic criteria recommended by the Research Committee on MMD of the Ministry of Health and Welfare of Japan in 2012.
- Suzuki stage: 2-5 stage
- Age: between 18 and 65 years old
- Subjects present with ischemic stroke or transient ischemic attack.
- Subjects who plan to accept the first EDAS surgery.
- Informed consent obtained from patient or patient's surrogate
Exclusion Criteria:
- Acute ischemic stroke occurred within one month.
- Suffered Intracranial hemorrhage before
- Subjects with large infarction spread widely over the territory of a main arterial trunk
- Aneurysms in the main arterial trunk
- Severe cardiac diseases like atrial fibrillation，valvular disease，heart failure, infective endocarditis and so on.
- Malignant tumors or severe disordered function of the heart, lung, liver or kidney.
- Severe hemostatic disorder or severe coagulation dysfunction.
- Uncontrolled diabetes mellitus with a serum fasting blood glucose level>300 mg/dL, or requires insulin; hypertension with a systolic blood pressure over 180 mmHg or a diastolic blood pressure over 110 mmHg.
- Severe injury on upper limbs.
- Pregnant or lactating women.
- Life expectancy is less than 3 years.
- Patients who are not suitable for this trial considered by researchers for other reasons
Sites / Locations
- The 307th Hospital of the Chinese People's Liberation ArmyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
RIC group
control group
Arm Description
Patients who are allocated into RIC group will undergo the first EDAS surgery combined 3-month remote ischemic conditioning (RIC) treatment. The opposite operation will be performed at 3 months after the first operation. RIC is a non-invasive therapy that performed by an electric auto-control device with cuff placed on arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuff on one arm. EDAS involves placement of an external carotid artery branch beneath the dura in the ischemic territories. The superficial temporal artery (STA) was commonly used.
Patients who are allocated into the control group will accept EDAS surgery twice. The second operation will be performed at 3 months after the first operation. EDAS involves placement of an external carotid artery branch beneath the dura in the ischemic territories. The superficial temporal artery (STA) was commonly used. Under certain circumstances, depending on the territory at risk, the occipital artery was also used. The donor vessel with the strip of galea (the arterial bridge) was detached from the pericranium or the fascia below, and two burr holes are made beneath the proximal and distal ends of the arterial bridge. The burr holes, with an average size of 3.0 × 8.0 cm, were connected by mill to make an oval bone flap and the dura was exposed. The target artery was then sewn to the dura using 10-0 Prolene suture. The bone flap was closed after cutting out the entry and exit sites for the target artery.
Outcomes
Primary Outcome Measures
rCBF changed ratio at operative side
Cerebral blood flow will be evaluated by dynamic susceptibility contrast-MRI examination，and relative cerebral blood flow(rCBF) changed ratio will be calculated by the formula: (rCBF in MCA territory/rCBF in cerebellum after treatment - rCBF in MCA territory/rCBF in cerebellum before treatment )/ rCBF in MCA territory/rCBF in cerebellum before treatment (the operative side). The higher value of rCBF improvement ratio means better imaging outcome.
Secondary Outcome Measures
the change of TTP delay at operative side
Time to peak(TTP) will be evaluated by dynamic susceptibility contrast-MRI examination. The improvement of TTP delay at operative side will be calculated by the formula: the change of TTP delay =TTP delay in MCA territory before treatment - TTP delay in MCA territory after treatment (the operative side). The higher value means better imaging outcome.
rCBF changed ratio at non-operative side
Cerebral blood flow will be evaluated by dynamic susceptibility contrast-MRI examination，and relative cerebral blood flow(rCBF) changed ratio will be calculated by the formula: (rCBF in MCA territory/rCBF in cerebellum after treatment - rCBF in MCA territory/rCBF in cerebellum before treatment )/ rCBF in MCA territory/rCBF in cerebellum before treatment (the non-operative side). The higher value of rCBF improvement ratio means better imaging outcome.
the change of TTP delay at non-operative side
Time to peak(TTP) will be evaluated by dynamic susceptibility contrast-MRI examination. The improvement of TTP delay at non-operative side will be calculated by the formula: Improvement of TTP delay =TTP delay in MCA territory before treatment - TTP delay in MCA territory after treatment (the non-operative side). The higher value means better imaging outcome.
Incidence of major adverse cerebral event ( MACE)
MACE contains ischemic or hemorrhagic stroke, crescendo TIAs evaluated by registered Neurologists.
The change of luminal area of superficial temporal artery
The luminal area of STA can reflect the angiogenesis induced by EDAS to some extent, and it will be measured by TOF-MRA.
The degree of the collaterals from superficial temporal artery
The degree of the collaterals from superficial temporal artery will be evaluated by Transcranial Doppler ultrasound performed by an experienced technician. 0 for no collaterals from STA, 1 for little collaterals from STA, 2 for good collaterals from STA .
Volume of regions with hyperintense signal
Volume of regions with hyperintense signal where the maximum dimension should be larger than 8mm will be measured at axial T2, fluid-attenuated inversion recovery.
Number of regions with hyperintense signal
Number of regions with hyperintense signal will be counted at axial T2, fluid-attenuated inversion recovery.
RIC related Adverse events
Adverse events related to RIC treatment, such as local edema, erythema, skin lesions of the arms.
Flow velocity of superficial temporal artery at operative side
Flow velocity of superficial temporal artery at operative side will be evaluated by Transcranial Doppler ultrasound performed by an experienced technician.
Full Information
NCT ID
NCT04917003
First Posted
June 1, 2021
Last Updated
June 27, 2021
Sponsor
Capital Medical University
Collaborators
Beijing 302 Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04917003
Brief Title
Safety and Efficacy of Remote Ischemic Conditioning Combined EDAS on Ischemic Moyamoya Disease
Acronym
RIC-IMD
Official Title
Safety and Efficacy of Remote Ischemic Conditioning Combined Encephaloduroarteriosynangiosis（EDAS）on Ischemic Moyamoya Disease: A Prospective, Randomized, Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
June 15, 2021 (Actual)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
June 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Capital Medical University
Collaborators
Beijing 302 Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Encephaloduroarteriosynangiosis (EDAS) is widely used as an indirect technique for treatment of moyamoya disease. Nevertheless, this indirect surgery tends to establish insufficient collateral circulation in most adult MMD patients. Nowadays, there is a lack of adjuvant therapies for improving collateral circulation induced by indirect revascularization. This study aims to explore whether remote ischemic conditioning can improve the collateral circulation after indirect revascularization.
Detailed Description
Encephaloduroarteriosynangiosis (EDAS) is widely used as an indirect technique for treatment of moyamoya disease. Nevertheless, this indirect surgery tends to establish insufficient collateral circulation in most adult MMD patients. Nowadays, there is a lack of adjuvant therapies for improving collateral circulation induced by indirect revascularization. Remote ischemic conditioning (RIC) is a noninvasive approach protecting the brain by inflating and deflating blood-pressure cuff placed on the upper limbs. It has been confirmed to improve cerebral perfusion by promoting angiogenesis and arteriogenesis in ischemic animal brain. In addition, daily remote ischemic conditioning is a promising technique to ameliorate chronic cerebrovascular disease like intracranial atherosclerotic stenosis, small-vessel disease.
Thus, this study aims to explore whether remote ischemic conditioning can improve the collateral circulation after indirect revascularization.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Moyamoya Disease
Keywords
moyamoya disease, EDAS, remote ischemic conditioning, cerebral blood flow
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RIC group
Arm Type
Experimental
Arm Description
Patients who are allocated into RIC group will undergo the first EDAS surgery combined 3-month remote ischemic conditioning (RIC) treatment. The opposite operation will be performed at 3 months after the first operation.
RIC is a non-invasive therapy that performed by an electric auto-control device with cuff placed on arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuff on one arm.
EDAS involves placement of an external carotid artery branch beneath the dura in the ischemic territories. The superficial temporal artery (STA) was commonly used.
Arm Title
control group
Arm Type
Other
Arm Description
Patients who are allocated into the control group will accept EDAS surgery twice. The second operation will be performed at 3 months after the first operation.
EDAS involves placement of an external carotid artery branch beneath the dura in the ischemic territories. The superficial temporal artery (STA) was commonly used. Under certain circumstances, depending on the territory at risk, the occipital artery was also used. The donor vessel with the strip of galea (the arterial bridge) was detached from the pericranium or the fascia below, and two burr holes are made beneath the proximal and distal ends of the arterial bridge. The burr holes, with an average size of 3.0 × 8.0 cm, were connected by mill to make an oval bone flap and the dura was exposed. The target artery was then sewn to the dura using 10-0 Prolene suture. The bone flap was closed after cutting out the entry and exit sites for the target artery.
Intervention Type
Other
Intervention Name(s)
RIC plus EDAS
Intervention Description
Patients who are allocated into RIC group will undergo EDAS surgery combined 3-month RIC treatment. The opposite operation will be performed at 3 months after the first operation.
Intervention Type
Other
Intervention Name(s)
EDAS
Intervention Description
Patients who are allocated into the control group will accept EDAS surgery twice. The second operation will be performed at 3 months after the first operation.
Primary Outcome Measure Information:
Title
rCBF changed ratio at operative side
Description
Cerebral blood flow will be evaluated by dynamic susceptibility contrast-MRI examination，and relative cerebral blood flow(rCBF) changed ratio will be calculated by the formula: (rCBF in MCA territory/rCBF in cerebellum after treatment - rCBF in MCA territory/rCBF in cerebellum before treatment )/ rCBF in MCA territory/rCBF in cerebellum before treatment (the operative side). The higher value of rCBF improvement ratio means better imaging outcome.
Time Frame
From baseline to 3 months.
Secondary Outcome Measure Information:
Title
the change of TTP delay at operative side
Description
Time to peak(TTP) will be evaluated by dynamic susceptibility contrast-MRI examination. The improvement of TTP delay at operative side will be calculated by the formula: the change of TTP delay =TTP delay in MCA territory before treatment - TTP delay in MCA territory after treatment (the operative side). The higher value means better imaging outcome.
Time Frame
From baseline to 3 months.
Title
rCBF changed ratio at non-operative side
Description
Cerebral blood flow will be evaluated by dynamic susceptibility contrast-MRI examination，and relative cerebral blood flow(rCBF) changed ratio will be calculated by the formula: (rCBF in MCA territory/rCBF in cerebellum after treatment - rCBF in MCA territory/rCBF in cerebellum before treatment )/ rCBF in MCA territory/rCBF in cerebellum before treatment (the non-operative side). The higher value of rCBF improvement ratio means better imaging outcome.
Time Frame
From baseline to 3 months.
Title
the change of TTP delay at non-operative side
Description
Time to peak(TTP) will be evaluated by dynamic susceptibility contrast-MRI examination. The improvement of TTP delay at non-operative side will be calculated by the formula: Improvement of TTP delay =TTP delay in MCA territory before treatment - TTP delay in MCA territory after treatment (the non-operative side). The higher value means better imaging outcome.
Time Frame
From baseline to 3 months.
Title
Incidence of major adverse cerebral event ( MACE)
Description
MACE contains ischemic or hemorrhagic stroke, crescendo TIAs evaluated by registered Neurologists.
Time Frame
From baseline to 3 months.
Title
The change of luminal area of superficial temporal artery
Description
The luminal area of STA can reflect the angiogenesis induced by EDAS to some extent, and it will be measured by TOF-MRA.
Time Frame
From baseline to 3 months.
Title
The degree of the collaterals from superficial temporal artery
Description
The degree of the collaterals from superficial temporal artery will be evaluated by Transcranial Doppler ultrasound performed by an experienced technician. 0 for no collaterals from STA, 1 for little collaterals from STA, 2 for good collaterals from STA .
Time Frame
From baseline to 3 months.
Title
Volume of regions with hyperintense signal
Description
Volume of regions with hyperintense signal where the maximum dimension should be larger than 8mm will be measured at axial T2, fluid-attenuated inversion recovery.
Time Frame
From baseline to 3 months.
Title
Number of regions with hyperintense signal
Description
Number of regions with hyperintense signal will be counted at axial T2, fluid-attenuated inversion recovery.
Time Frame
From baseline to 3 months.
Title
RIC related Adverse events
Description
Adverse events related to RIC treatment, such as local edema, erythema, skin lesions of the arms.
Time Frame
From baseline to 3 months.
Title
Flow velocity of superficial temporal artery at operative side
Description
Flow velocity of superficial temporal artery at operative side will be evaluated by Transcranial Doppler ultrasound performed by an experienced technician.
Time Frame
From baseline to 3 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects who were diagnosed as moyamoya disease by the diagnostic criteria recommended by the Research Committee on MMD of the Ministry of Health and Welfare of Japan in 2012.
Suzuki stage: 2-5 stage
Age: between 18 and 65 years old
Subjects present with ischemic stroke or transient ischemic attack.
Subjects who plan to accept the first EDAS surgery.
Informed consent obtained from patient or patient's surrogate
Exclusion Criteria:
Acute ischemic stroke occurred within one month.
Suffered Intracranial hemorrhage before
Subjects with large infarction spread widely over the territory of a main arterial trunk
Aneurysms in the main arterial trunk
Severe cardiac diseases like atrial fibrillation，valvular disease，heart failure, infective endocarditis and so on.
Malignant tumors or severe disordered function of the heart, lung, liver or kidney.
Severe hemostatic disorder or severe coagulation dysfunction.
Uncontrolled diabetes mellitus with a serum fasting blood glucose level>300 mg/dL, or requires insulin; hypertension with a systolic blood pressure over 180 mmHg or a diastolic blood pressure over 110 mmHg.
Severe injury on upper limbs.
Pregnant or lactating women.
Life expectancy is less than 3 years.
Patients who are not suitable for this trial considered by researchers for other reasons
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xunming Ji, PhD
Phone
861013120136877
Email
jixunming@vip.163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jiali Xu, MD
Phone
010-18800117908
Email
m18800117908@163.com
Facility Information:
Facility Name
The 307th Hospital of the Chinese People's Liberation Army
City
Beijing
ZIP/Postal Code
100071
Country
China
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of Remote Ischemic Conditioning Combined EDAS on Ischemic Moyamoya Disease
We'll reach out to this number within 24 hrs