The Safety and Efficacy of RIC on Adult Moyamoya Disease (RIC-AMD)

The Safety and Effect of Remote Ischemic Conditioning on Adult Moyamoya Disease

There are a series of symptoms such as ischemic stroke、transient ischemic attack 、hemorrhagic stroke、headache 、seizure and so on in moyamoya disease( MMD) patients .Nowadays, revascularization is the only effective way for ischemic MMD and there is no effective conservative treatment for MMD. This study was to explore the safety and efficacy of remote ischemic conditioning(RIC ) on adult MMD patients.

Study Overview

• Status: Completed
• Conditions: Moyamoya Disease
• Intervention / Treatment: Device: RIC; Drug: Aspirin

Detailed Description

There are a series of symptoms such as ischemic stroke、transient ischemic attack 、hemorrhagic stroke、headache 、seizure and so on in moyamoya disease. Nowadays, revascularization is the only effective way for ischemic MMD while controversial for hemorrhagic MMD patients. Surgical complications including hyperperfusion syndrome, cerebral infarction or bleeding often occurred postoperatively. There is no effective conservative treatment for MMD up to now.

Remote ischemic conditioning is Remote ischemic conditioning (RIC) is a noninvasive and easy-to-use neuroprotective strategy, and it has potential effects on preventing ischemia reperfusion injury and ischemic infarction.This study was to explore the safety and efficacy of remote ischemic conditioning on adult MMD patients.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18-60 years
• All of the patients underwent digital subtraction angiography (DSA) and met the current diagnostic criteria recommended by the Research Committee on MMD of the Ministry of Health and Welfare of Japan in 2012.
• mRs≤3
• Informed consent obtained from patient or acceptable patient's surrogate.

Exclusion Criteria:

• Patients with acute ischemic or hemorrhagic stroke within 3 months.
• Severe hepatic or renal dysfunction.
• Severe hemostatic disorder or severe coagulation dysfunction.
• Severe cardiac diseases.
• Patients with severe existing neurological or psychiatric disease
• Patients with moyamoya syndrome caused by autoimmune disease, Down syndrome , neurofibromatosis, leptospiral infection, or previous skull-base radiation therapy.
• Patients have been done or plan to accept revascularization surgery.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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. They will also accept medication treatment by professional neurologists.	Device: RIC; 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.
Other: Medication group; Patients allocated to Medication group will accept medication treatment by professional neurologists.	Drug: Aspirin; patients will accept medication guided by neurologists

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
improvement ratio of mean cerebral blood flow	Cerebral blood flow refers to the flow of blood through a certain cross-sectional area of cerebrovascular in a unit time. Patients' CBF will be detected by arterial spin labeling. In each hemisphere, middle cerebral artery territory was divided into ten regions according to Albert Stroke Program Early CT score (ASPECTS), regions of interest (ROI) were drawn manually in each of territory of MCA to determine the absolute CBF values. improvement ratio of mean CBF= mCBF atter treatment-mCBF baseline/mCBF baseline.	change from the baseline to12 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of ischemic stroke	ischemic stroke is diagnosed by symptoms of neurologic deficit or head CT and MRI.	from the baseline to 12 months after treatment
incidence of transient ischemic attack	TIA is diagnosed by patients' transient neurologic deficit	from the baseline to 12 months after treatment
incidence of hemorrhagic stroke	hemorrhagic stroke is diagnosed by head CT	from the baseline to 12 months after treatment
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	change from the baseline to 3, 6, 12 months after treatment
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	change from the baseline to 3, 6, 12 months after treatment
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	change from the baseline to 3, 6 ,12 months after treatment
The rate of death and adverse event	All causes of death will be included to compute mortality at 12 months after therapy	change from the baseline to 12 months after treatment
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.	change from the baseline to 12 months after treatment
The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure	the investigator will record the number.	change from the baseline to 12 months after treatment
The rate of progression of stenosis or occlusion at Willis circle	Progression of stenosis or occlusion at Willis circle was evaluated by TOF-MRA, which was defined as the the stenosis or occlusion was progressed to another part of Willis circle, like stenosis progressed from M1 to M2-M4 et al, or in the same part, stenosis progressed to occlusion.	12 months after therapy

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): November 10, 2020
• Study Completion (Actual): February 2, 2021

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: July 7, 2019
• First Posted (Actual): July 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: remote ischemic conditioning; cerebral blood flow; moyamoya disease
• Additional Relevant MeSH Terms: 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; Moyamoya Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: RIC-AMD

Drug and device information, study documents

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