Remote Ischemic Conditioning for Chronic Cerebral Artery Occlusion

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Chronic Cerebral Artery Occlusion: A Prospective, Randomized, Controlled Study

Chronic cerebral artery occlusion (CCAO), which is characterized by the pathophysiological change of long-term cerebral hemodynamic disorder, is one of the major risk factors affect the occurrence and recurrence of ischemic stroke. However, the mechanism of CCAO injury is not clear and effective treatment is warranted. The purpose of this study is to investigate the protective effect and underlying mechanism of remote ischemic conditioning (RIC) on CCAO.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Artery Occlusion
• Intervention / Treatment: Device: Remote ischemic conditioning

Detailed Description

CCAO is a cerebrovascular disease due to cerebral hypo-perfusion. It is often associated with repeated ischemic stroke or transient neurological symptoms, progressive cognitive decline and reduction of daily ability. Specific and effective treatment is warranted for symptomatic management of CCAO. RIC is a non-invasive strategy to protect the brain. The clinical trials have demonstrated that daily limb RIC seems to be potentially effective in patients with symptomatic intracranial arterial stenosis in cerebral blood flow and metabolism. RIC can also ameliorate cerebral small vessel disease in slowing cognition decline and reducing white matter. Therefore, it is worth to investigate the neuroprotective mechanism of RIC for CCAO.

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

Contacts and Locations

• Study Contact: Name: Hongrui Ma, MD; Phone Number: 17319359172; Email: beif1995@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Xuanwu Hospital Capital Medical University
    • Contact: Hongrui Ma; Phone Number: 17319359172; Email: beif1995@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) Age range 40-80 years, regardless of gender;
• (2) Digital angiography (DSA) / ultrasound / CT angiography (CTA) / magnetic resonance angiography (MRA) showed unilateral internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion and stenosis of any other cerebral arteries (e.g. the other side of ICA or MCA, basilar artery) < 50%;
• (3) Modified Rankin Scale (mRS) score 0-2;
• (4) Symptoms of ischemic cerebrovascular disease (ischemic stroke or TIA) due to ICA or MCA occlusions within 12 months prior to enrollment;
• (5) neurological deficits were stable ≥ 30 days after occlusion;
• (6) Magnetic resonance perfusion weighted imaging (PWI) showed mean transit time (MTT) ≥ 4s and related cerebral blood flow (rCBF) (symptomatic side/asymptomatic side) < 0.95;
• (7) The subject or its legally authorized representative is able to provide informed reports.

Exclusion Criteria:

• (1) Uncontrolled hypertension despite the use of antihypertensive drugs before enrollment (defined as systolic blood pressure ≥200mmHg);
• (2) Stenosis or occlusion of subclavian artery and upper limb artery;
• (3) Previous history of cerebral hemorrhage, including intracranial hemorrhage, ischemic stroke hemorrhage transformation, vascular malformation or intracranial tumor or other parts of the active bleeding disease;
• (4) History of brain tumor or mental illness or acute stroke ≤6 months;
• (5) Suffering from cardiogenic thrombosis diseases, such as mitral stenosis and atrial fibrillation, myocardial infarction, mural thrombosis or valvular vegetations, congestive heart failure or endocarditis within six months;
• (6) Obvious disorder of coagulation mechanism;
• (7) Severe liver or kidney insufficiency, malignant tumor, or serious diseases requiring medical intervention or surgery;
• (8) There is soft tissue or blood vessel injury at the cuff compression site of RIC treatment, or other conditions that cannot tolerate RIC;
• (9) Pregnant or lactating women;
• (10) Life expectancy <6 months;
• (11) Refusal to sign informed consent, poor compliance, or inability to complete complete treatment, etc.

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
Experimental: RIC group; Participants in the experimental group receive both RIC and standard clinical therapy. The RIC treatment is composed of 5 cycles of bilateral upper limb ischemia for 5 minutes followed by reperfusion for another 5 minutes performed twice a day for a total of 180 consecutive days.The procedure was performed by using an electric autocontrol device with cuffs that inflated to a pressure of 200 mmHg during the ischemic period and deflated during the reperfusion (Patent No.CN200820123637.X, China).	Device: Remote ischemic conditioning; The LRIC treatment consisted of 5 cycles of bilateral upper limb ischemia for 5 minutes followed by reperfusion for another 5 minutes performed twice a day for a total of 180 consecutive days.The procedure was performed by using an electric autocontrol device with cuffs that inflated to a pressure of 200 mmHg during the ischemic period and deflated during the reperfusion.(Patent No.CN200820123637.X, China).
No Intervention: Control group; Participants in the control group receive standard clinical therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of cerebral blood flow perfusion	The investigators evaluate the change of perfusion capacity of cerebral blood vessels on PWI-MRI.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence times of stroke or transient ischemic attack (TIA)	The investigators evaluate the times of stroke or transient ischemic attack (TIA) recurrence.	180 days
Changes of volume of WMHs	The investigators evaluate the the change of volume of WMHs on Flairs-MRI.	180 days
Change of the direction of white matter cellulose	The investigators evaluate the change of direction of white matter cellulose on DTI-MRI.	180 days
Change of cerebral hemoglobin oxygenation status	The investigators evaluate the change of cerebral hemoglobin oxygenation status on BOLD-rsfMRI.	180 days
Change of collateral circulation	The investigators evaluate the change of collateral circulation on ASL-MRI.	180 days
Change of the Montreal Cognitive Assessment (MoCA) score	The investigators evaluate the change of neurobehavioral function by the Montreal Cognitive Assessment (MoCA) score. The minimum value is 0 and maximum value is 30. The higher scores represent the better outcome.	180 days
Change of the Verbal Fluency Test (VFT) score	The investigators evaluate the change of neurobehavioral function by the Verbal Fluency Test (VFT) score. The minimum value is 0 and without the maximum value. The higher scores represent the better outcome.	180 days
Change of the Digit Span Forward and Backward score	The investigators evaluate the change of neurobehavioral function by the Digit Span Forward and Backward score. The minimum value is 3 and maximum value is 12. The higher scores represent the better outcome.	180 days
Change of the Hamilton Depression-17 (HAMD-17) scale	The investigators evaluate the change of neuropsychological function by the Hamilton Depression-17 (HAMD-17) scale. The minimum value is 0 and maximum value is 54. The higher scores represent the worse outcome.	180 days
Change of the Hamilton Anxiety (HAMA) scale	The investigators evaluate the change of neuropsychological function by the Hamilton Anxiety (HAMA) scale. The minimum value is 0 and maximum value is 56. The higher scores represent the worse outcome.	180 days
Adverse events related to RIC treatment	Adverse events related to RIC treatment, such as mucocutaneous hemorrhage, changes in coagulation function and so on.	From baseline to 180-day treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of RIC [Number of patients not tolerating RIC procedure and patients with erythema or skin lesions related to RIC]	The safety of RIC by the number of patients not tolerating RIC procedure and patients with erythema or skin lesions related to RIC.	180 days

Collaborators and Investigators

• Sponsor: Capital Medical University

Publications and helpful links

General Publications

• Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012 Oct 30;79(18):1853-61. doi: 10.1212/WNL.0b013e318271f76a. Epub 2012 Oct 3.
• Wang Y, Meng R, Song H, Liu G, Hua Y, Cui D, Zheng L, Feng W, Liebeskind DS, Fisher M, Ji X. Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease. Stroke. 2017 Nov;48(11):3064-3072. doi: 10.1161/STROKEAHA.117.017691. Epub 2017 Oct 17.

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2022
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Actual): May 16, 2022
• Last Update Submitted That Met QC Criteria: May 13, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases
• Other Study ID Numbers: RIC-CCAO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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