Effects of Remote Ischemic Conditioning on Dynamic Cerebral Autoregulation, Blood Pressure and Heart Rate Variability in Patients With Cerebral Small Vessel Disease (ESCAPE-SVD)

The purpose of this study is to determine effects of remote ischemic conditioning on dynamic cerebral autoregulation, blood pressure and heart rate variability in patients with cerebral small vessel disease.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Small Vessel Diseases
• Intervention / Treatment: Procedure: Remote ischemic conditioning; Procedure: Sham remote ischemic conditioning

Detailed Description

In this study, 100 cases of cerebral small vessel disease in the First Hospital of Jilin University are divided into 2 groups according to the intention of the individual. On the basis of standard medical treatment, the experimental group receive in-hospital remote ischemic conditioning treatment for 200 mmHg, 2 times per day; the control group receive remote ischemic conditioning for 60 mmHg, 2 times per day during the period of hospitalization. Patients in both groups undergo several dynamic cerebral autoregulation and beat-to-beat monitoring respectively at baseline, 3-4 days of remote ischemic conditioning and the time the last in-hospital remote ischemic conditioning performed. Two groups will be followed up for 90 days to evaluate the effects of remote ischemic conditioning therapy.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yi Yang, MD, PhD; Phone Number: 0086-13756661217; Email: doctor_yangyi@163.com
• Study Contact Backup: Name: Zhen-Ni Guo, MD; Email: zhen1ni2@163.com

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: Yi Yang, MD, PhD; Email: doctor_yangyi@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) Regardless of age, sex;

• 2) Patients are diagnosed with cerebral small vessel disease, and neuroimaging shows new subcortical lacunar infarction (in line with one of the following):

  ① MRI examination Diffusion-weighted imaging (DWI) phase shows high signal intensity [Apparent Diffusion Coefficient (ADC) diffusion restriction] lesions < 20 mm diameter in subcortical, basal ganglia or brainstem , with or without corresponding clinical symptoms;

  ② With new clinical symptoms, MRI examination FLAIR sequence shows corresponding FLAIR high signal intensity lesions [diameter < 20 mm]) in subcortical, basal ganglia or pons;

• 3) Remote ischemic conditioning can be started within 7 days from onset;
• 4) Willing to participate and sign the informed consent.

Exclusion Criteria:

• 1) Vascular stenosis > 50% by Transcranial Doppler (TCD);
• 2) Previous history of intracranial hemorrhage or major bleeding in other parts of the body;
• 3) Previous history of atrial fibrillation or myocardial infarction within 6 months;
• 4) Moyamoya disease or hereditary cerebral small vessel disease, such as mitochondrial encephalopathy, CADASIL or Fabry;
• 5) The patients who had clear non-vascular white matter lesions, such as multiple sclerosis, adult white matter dysplasia, metabolic encephalopathy;
• 6) Severe hepatic and renal diseases, cancer or other major diseases related to medical and surgical procedures;
• 7) The patients who had the contraindication of remote ischemic conditioning treatment, such as severe soft tissue injury, fracture or vascular injury in the upper limb; Acute or subacute venous thrombosis, arterial occlusive disease, subclavian steal syndrome, etc;
• 8) Significant coagulation abnormalities;
• 9) Pregnant or lactating women;
• 10) The patients with disturbance of consciousness or agitation who cannot cooperate to dynamic cerebral autoregulation monitoring or beat-to-beat blood pressure monitoring;
• 11) Previous remote ischemic conditioning therapy or similar treatment;
• 12) Unwilling to be followed up or treated for poor compliance;
• 13) He/She is participating in other clinical research or has participated in other clinical research or has participated in this study within 3 months prior to admission;
• 14) Other conditions that the researchers think are not suitable for the group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RIC+Standard medical treatment; Remote ischemic conditioning (RIC) is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 200 mmHg. RIC will be conducted twice daily during the period of hospitalization. Besides, the patients will be treated with standard medical treatment according to consensus on diagnosis and treatment of cerebral small vessel disease in China 2015, including antiplatelet aggregation and lipid-stabilizing drugs as well as neurotrophic and circulation improving treatment.	Procedure: Remote ischemic conditioning; Remote ischemic conditioning (RIC) is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 200 mmHg. RIC will be conducted twice daily during the period of hospitalization.
Placebo Comparator: Sham RIC+Standard medical treatment; Remote ischemic conditioning (RIC) is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 60 mmHg. RIC will be conducted twice daily during the period of hospitalization. Besides, the patients will be treated with standard medical treatment according to consensus on diagnosis and treatment of cerebral small vessel disease in China 2015, including antiplatelet aggregation and lipid-stabilizing drugs as well as neurotrophic and circulation improving treatment.	Procedure: Sham remote ischemic conditioning; Remote ischemic conditioning (RIC) is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 60 mmHg. RIC will be conducted twice daily during the period of hospitalization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Difference(PD) in Degree	PD is a dynamic cerebral auto-regulation parameter derived from transfer function analysis.	within 7 days of RIC
Differences of blood pressure variability (BPV) in Degree after in-hospital remote ischemic conditioning finished between two groups	BPV is defined as blood pressure oscillations in relation to the mean values.	within 7 days of RIC
Differences of heart rate variability (HRV) in Degree after in-hospital remote ischemic conditioning finished between two groups	HRV is defined as heart rate oscillations in relation to the mean values.	within 7 days of RIC

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of BPV in Degree after 3-4 days remote ischemic conditioning treatment between two groups	BPV is defined as blood pressure oscillations in relation to the mean values.	3-4 days after RIC
Differences of HRV in Degree after 3-4 days remote ischemic conditioning treatment between two groups	HRV is defined as heart rate oscillations in relation to the mean values.	3-4 days after RIC
PD in Degree	PD is a dynamic cerebral auto-regulation parameter derived from transfer function analysis.	3-4 days after RIC
Differences in modified Rankin Scale (mRS) Score between two groups	Modified Rankin Scale (mRS) Score ranged from 0 to 6, a low value represents a better outcome.	3 months

Collaborators and Investigators

• Sponsor: Yi Yang

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2021
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: December 9, 2021
• First Submitted That Met QC Criteria: January 25, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases
• Other Study ID Numbers: ESCAPE-SVD

Drug and device information, study documents

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