Safety and Efficacy of Remote Ischemic Conditioning Combined EDAS on Ischemic Moyamoya Disease (RIC-IMD)

Safety and Efficacy of Remote Ischemic Conditioning Combined Encephaloduroarteriosynangiosis（EDAS）on Ischemic Moyamoya Disease: A Prospective, Randomized, Controlled Study

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.

Study Overview

• Status: Recruiting
• Conditions: Moyamoya Disease
• Intervention / Treatment: Other: RIC plus EDAS; Other: EDAS

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xunming Ji, PhD; Phone Number: 861013120136877; Email: jixunming@vip.163.com
• Study Contact Backup: Name: Jiali Xu, MD; Phone Number: 010-18800117908; Email: m18800117908@163.com

Study Locations

• China
  • Beijing, China, 100071
    • Recruiting
    • The 307th Hospital of the Chinese People's Liberation Army

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Suzuki stage: 2-5 stage
3. Age: between 18 and 65 years old
4. Subjects present with ischemic stroke or transient ischemic attack.
5. Subjects who plan to accept the first EDAS surgery.
6. Informed consent obtained from patient or patient's surrogate

Exclusion Criteria:

1. Acute ischemic stroke occurred within one month.
2. Suffered Intracranial hemorrhage before
3. Subjects with large infarction spread widely over the territory of a main arterial trunk
4. Aneurysms in the main arterial trunk
5. Severe cardiac diseases like atrial fibrillation，valvular disease，heart failure, infective endocarditis and so on.
6. Malignant tumors or severe disordered function of the heart, lung, liver or kidney.
7. Severe hemostatic disorder or severe coagulation dysfunction.
8. 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.
9. Severe injury on upper limbs.
10. Pregnant or lactating women.
11. Life expectancy is less than 3 years.
12. Patients who are not suitable for this trial considered by researchers for other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RIC group; 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.	Other: RIC plus EDAS; 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.
OTHER: control group; 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.	Other: EDAS; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline to 3 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline to 3 months.
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.	From baseline to 3 months.
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.	From baseline to 3 months.
Incidence of major adverse cerebral event ( MACE)	MACE contains ischemic or hemorrhagic stroke, crescendo TIAs evaluated by registered Neurologists.	From baseline to 3 months.
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.	From baseline to 3 months.
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 .	From baseline to 3 months.
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.	From baseline to 3 months.
Number of regions with hyperintense signal	Number of regions with hyperintense signal will be counted at axial T2, fluid-attenuated inversion recovery.	From baseline to 3 months.
RIC related Adverse events	Adverse events related to RIC treatment, such as local edema, erythema, skin lesions of the arms.	From baseline to 3 months.
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.	From baseline to 3 months.

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2021
• Primary Completion (ANTICIPATED): June 30, 2022
• Study Completion (ANTICIPATED): June 30, 2022

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (ACTUAL): June 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 27, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: remote ischemic conditioning; cerebral blood flow; moyamoya disease; EDAS
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Carotid Artery Diseases; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Ischemia; Moyamoya Disease
• Other Study ID Numbers: RIC-IMD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No