Effects of Remote Ischemic Pre-Conditioning in Moyamoya Disease Patients (RIME)

Effects of Remote Ischemic Pre-Conditioning on Neurologic Complications in Adult Ischemic Moyamoya Disease Patients Undergoing Encephaloduroarteriosynangiosis

In the present study, investigators evaluated whether RIPC reduce the major neurological complications in adult moyamoya disease patients undergoing encephaloduroarteriosynangiosis (EDAS).

Study Overview

• Status: Suspended
• Conditions: Moyamoya Disease; Remote Ischemic Preconditioning
• Intervention / Treatment: Procedure: Sham remote ischemic preconditioning; Procedure: Encephaloduroarteriosynangiosis; Procedure: Remote ischemic preconditioning

Detailed Description

BACKGROUND: Brain ischemia and injury contributed to perioperative morbidity and mortality in revascularization surgery. Remote ischemic preconditioning (RIPC), brief periods of ischemia followed by reperfusion, can provide systemic protection for prolonged ischemia. Previous study found combined remote ischemic pre- and post-conditioning can be effective in reducing neurologic complications and the duration of hospitalization in moyamoya patients undergoing direct revascularization.In order to investigate whether RIPC before EDAS can protect these patients from the perioperative and long-term complications, a prospective randomized controlled trial will be performed in the current study.

DESIGNING: About 328 patients who are eligible for carotid artery stenting will be randomly assigned in 1:1 ratio to RIPC group and sham RIPC group (control). Remote limb ischemic preconditioning (RIPC) is consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, it is induced by a sphygmomanometer placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min, patients in the RIPC group will do it twice a day for at least five days before EDAS. Patients in the sham RIPC group receive sham RIPC treatment, which is consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, induced by a sphygmomanometer placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min, they will do it twice a day for at least five days before EDAS. Cerebral injury is assessed by plasma Human Soluble protein-100B (S-100B) and Neuron specific enolase (NSE). Clinical outcomes are determined by cerebrovascular events (including ischemic stroke, transient ischemic attack (TIA), cerebral hemorrhage and transient neurological deficit) and death or dependent.

• Study Type: Interventional
• Enrollment (Anticipated): 328
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 102206
      • Peking University International Hospital
    • Beijing, Beijing, China, 100070
      • Beijing Tiantan Hosiptal

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. Patients who diagnosed with moyamoya disease
2. Adults 18 to 65 years of age
3. The onset symptoms manifested as ischemic symptoms (TIA or stroke) or atypical symptoms (headache, epilepsy or asymptomatic)
4. Able to receive the necessary imaging examination
5. Patients who pre-agreed to the study

Exclusion Criteria:

1. Prior cerebral hemorrhage history
2. Other brain or cerebrovascular disease
3. Previous history of revascularization surgery
4. Dependent (mRS > 2)
5. Receive other type of revascularization surgery
6. Peripheral blood vessel disease (especially subclavian arterial and upper limb artery stenosis or occlusion).
7. Patients who do not agree with the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham RIPC group; Treatment:Patients in this group received standard medical therapy and sham remote ischemic preconditioning treatment. Device:Sham RIPC consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by a sphygmomanometer placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min, each patient in Sham RIPC group do it twice a day for at least five days before encephaloduroarteriosynangiosis. Procedure: Encephaloduroarteriosynangiosis	Procedure: Sham remote ischemic preconditioning; Sham remote ischemic preconditioning consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by a sphygmomanometer placed on bilateral arm and inflated to 60 mmHg for 5-min followed by deflating the cuff for 5-min.; Other Names: Sham RIPC; Procedure: Encephaloduroarteriosynangiosis; Encephaloduroarteriosynangiosis is an indirect revascularization surgery of moyamoya disease; Other Names: EDAS
Experimental: RIPC group; Treatment:Patients in this group received standard medical therapy and remote ischemic preconditioning (RIPC) treatment. Device:RIPC consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by a sphygmomanometer placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min,each patient in the RIPC group do it twice a day for at least five days before encephaloduroarteriosynangiosis. Procedure: Encephaloduroarteriosynangiosis	Procedure: Encephaloduroarteriosynangiosis; Encephaloduroarteriosynangiosis is an indirect revascularization surgery of moyamoya disease; Other Names: EDAS; Procedure: Remote ischemic preconditioning; Remote ischemic preconditioning consisted of five 5-min cycles of bilateral arm ischemia/reperfusion, which is induced by a sphygmomanometer placed on bilateral arm and inflated to 200 mmHg for 5-min followed by deflating the cuff for 5-min.; Other Names: RIPC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Cerebrovascular Events.	Cerebrovascular events included ischemic stroke, transient ischemic attack (TIA), cerebral hemorrhage and hyperperfusion syndrome.	postoperative one month
Number of Patients Dependent or Death	Dependent included the modified Rankin Scale (mRS) > 2. Death included any reason caused death.	postoperative one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Severity of the Ischemic Stroke after Surgery	The severity of the ischemic stroke was evaluated by the white matter hyperintensities volume on the MRI, the neurological deficits duration and the Modified Rankin Scale (mRS) of patients.	postoperative one month
Number of Patients Occured Re-stroke at Follow-up Period	Re-stroke included ischemic stroke and hemorrhagic stroke.	6 months and 12 months after EDAS
Number of Patients Dependent or Death at Follow-up Period	Dependent included the modified Rankin Scale (mRS) > 2. Death included any reason caused death.	6 months and 12 months after EDAS
Number of Patients with Improved Neurological Function at Follow-up Period	The modified Rankin Scale (mRS) decreased at the follow-up period compared to preoperative scores	6 months and 12 months after EDAS
Perfusion Status of Patients at Follow-up Period	The perfusion status detected by stages of pre-infarction period based on computed tomography perfusion imaging	6 months and 12 months after EDAS
Number of Patients With Any Side Effects of Remote Ischemic Preconditioning (RIPC) Treatment.	The side effects referred to any side effects of RIPC or sham RIPC treatment, not including the sides effect of medications and EDAS.	From baseline to 12 months after treatment
Participants Who Got New Diffusion-weighted Imaging (DWI) Lesions on Post-treatment Magnetic Resonance Imaging (MRI) Scans.	The presence of ≥1 new brain lesions on DWI	Within 48 hours after EDAS

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Peking University International Hospital
• Investigators: Principal Investigator: Yuanli Zhao, MD, Beijing Tiantan Hospital; Principal Investigator: Rong Wang, MD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: August 20, 2019
• First Submitted That Met QC Criteria: August 20, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Ischemia; Cerebrovascular Disorders; Arterial Occlusive Diseases; Moyamoya Disease
• 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: RIPC2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The individual participant data (IPD) of this study are available from the principal investigator upon reasonable request.
• IPD Sharing Time Frame: 6 months after the study ended
• IPD Sharing Access Criteria: The IPD of this study are available from the principal investigator upon reasonable request.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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