Remote Ischemic Conditioning for Cerebral Ischemia in Patients With Takayasu Arteritis (TARIC-1) (TARIC-1)

Safety and Efficacy of Remote Ischemic Conditioning for Cerebral Ischemia in Patients With Takayasu Arteritis: a Prospective Cohort Study

The aim of this study is to evaluate the safety and efficacy of remote ischemic conditioning ( RIC ) in the protection of cerebral ischemia in patients with Takayasu arteritis ( TAK ). The study was designed as a prospective, double-blind, exploratory randomized controlled study. The entire study included a screening period and a treatment observation period ( a total of 24 weeks ). All patients with cerebral ischemia of TAK will be randomly divided into RIC group and sham RIC group at 1:1 ratio. On the basis of receiving the conventional drug therapy, the patients will be treated with RIC or sham RIC treatment twice daily for six month. The clinical data of patients at baseline and each follow-up will be collected, including basic information, disease activity assessment, laboratory indicators, imaging indicators, treatment data, adverse events, etc.The Primary outcome is the mean cerebral blood flow improvement rate ( mCBF-IR ) of TAK patients after 24 weeks-treatment. Secondary endpoints include the incidence of major adverse cerebrovascular events ( MACE ) , the change value of arterial transit time ( ATT ) in pCASL hypoperfusion area compared with baseline, occurrence of RIC-related adverse reactions, the changes of hematological indexes and disease activity score, etc. This study will provide insights into the preliminary proof of principle, safety, and efficacy of RIC in cerebral ischemia in patients with Takayasu arteritis ( TAK ), and this data will provide parameters for future larger scale clinical trials if efficacious.

Study Overview

• Status: Recruiting
• Conditions: Takayasu Arteritis; Cerebral Ischemia
• Intervention / Treatment: Device: RIC; Device: sham-RIC

Detailed Description

Clinical symptoms, routine follow-up laboratory tests, other serological indicators (VEGF, NGF, ET-1, ACE), PAF, PDGF, etc.), vascular involvement, cranial MRI, vascular injury score, disease activity and treatment will be collected at baseline. After RIC or sham RIC intervention, clinical symptoms, laboratory tests, disease activity, treatment and RIC-related adverse reactions will be collected at 1m, 2m,3m and 6m. the data of vascular involvement, cranial MRI, vascular injury score and disease activity will also be collected at 6 months follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yi Zhao, MD; Phone Number: +8613811038669; Email: zy85070@xwhosp.org
• Study Contact Backup: Name: Fang kong, MD; Phone Number: +8613051116280; Email: kongfang90@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Department of Rheumatology and Allergy, Xuanwu Hospital, Capital Medical University, Beijing, China
      • Contact: Yi Zhao, MD; Phone Number: 18618360999

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All patients fulfilled the 1990 American College of Rheumatology Classification Criteria for TAK
• Inactive state
• Male and female, aged 18-65 years old
• The presence of supra-aortic vascular involvement ( including but not limited to the left and right sides of the common carotid artery, subclavian artery, vertebral artery involvement )
• Decreased cerebral blood perfusion in the whole brain ( compared with healthy people ) or local ( left and right brain contrast ) suggested by pseudo-Continuous arterial spin labeling ( pCASL ) -MRI
• Voluntary participation in this study, signed informed consent

Exclusion Criteria:

• Complications that endanger the function of important organs, such as uncontrollable heart failure, severe heart valve disease, severe hypertension, severe myocardial ischemia, pulmonary hypertension, acute cerebral infarction, arterial dissection or aneurysm rupture, etc
• There are serious complications, such as poorly controlled diabetes, renal insufficiency, cardiopulmonary insufficiency, mental illness or malignant tumor
• There were moderate to severe stenosis of brachial artery in both upper limbs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RIC group; The RIC protocol includes five cycles of 5-min inflation to 200mmHg and 5-min deflation.	Device: RIC; RIC is a non-invasive therapy that is performed by automated pneumatic cuffs placed on unilateral arms. The RIC protocol includes five cycles of 5-min inflation to 200mmHg and 5-min deflation.
Sham Comparator: sham RIC group; The sham RIC protocol includes five cycles of 5-min inflation to 60mmHg and 5-min deflation.	Device: sham-RIC; Sham-RIC is a non-invasive therapy that is performed by automated pneumatic cuffs placed on unilateral arms. The sham RIC protocol includes five cycles of 5-min inflation to 60mmHg and 5-min deflation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean cerebral blood flow improvement rate	Mean cerebral blood flow improvement rate ( mCBF-IR ) of TAK patients will be obtained by pseudo-continuous arterial spin labeling ( pCASL ) -MRI.	during baseline to 6 months after therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of major adverse cerebrovascular events ( MACE )	MACEs are defined as the occurrence of stroke, transient ischemic attacks (TIAs), blindness in patients.	during baseline to 6 months after therapy
The change value of arterial transit time ( ATT )	The change value of arterial transit time ( ATT ) in pCASL hypoperfusion area compared with baseline	during baseline to 6 months after therapy
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.	during baseline to 6 months after therapy
The number of patients with palpation for tenderness related to RIC	Professional doctors will definite whether there's a palpation for tenderness and record the number.	during baseline to 6 months after therapy
The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure	The investigator will record the number.	during baseline to 6 months after therapy
The number of patients with any other adverse events related to RIC intervention	The investigator will record the number.	during baseline to 6months after therapy
Incidence of clinical symptoms	The investigator will observe and record the occurrence of the clinical symptoms of dizziness, limb claudication, pulse deficits, bruits, headache, neck pain, severe abdominal pain, hypertension, valvular insufficiency, arrhythmia, chest pain or dsypnea.	during baseline to 1, 2, 3, 6months after therapy
The change value of blood pressure (BP)	The change value of blood pressure (BP) will be compared with baseline	during baseline to 1, 2, 3, 6months after therapy
The change value of erythrocyte sedimentation rate (ESR)	The change value of erythrocyte sedimentation rate (ESR) will be compared with baseline	during baseline to 1, 2, 3, 6months after therapy
The change value of C reactive protein (CRP)	The change value of C reactive protein (CRP) will be compared with baseline	during baseline to 1, 2, 3, 6months after therapy
The change value of C reactive proteininterleukin 6 (IL-6)	The change value of interleukin 6 (IL-6) will be compared with baseline	during baseline to 1, 2, 3, 6months after therapy
The change value of serum level of vascular endothelial growth factor (VEGF)	The change values of serum level of vascular endothelial growth factor (VEGF) will be compared with baseline.	during baseline to 6months after therapy
The change value of serum level of nerve growth factor (NGF)	The change value of serum level of nerve growth factor (NGF) will be compared with baseline.	during baseline to 6months after therapy
The change value of serum level of endothelin-1 (ET-1)	The change value of serum level of endothelin-1 (ET-1) will be compared with baseline.	during baseline to 6months after therapy
The change value of serum level of angiotensin converting enzyme (ACE)	The change value of serum level of angiotensin converting enzyme (ACE) will be compared with baseline.	during baseline to 6months after therapy
The change value of serum level of platelet activating factor (PAF)	The change value of serum level of platelet activating factor (PAF) will be compared with baseline.	during baseline to 6months after therapy
The change value of serum level of platelet growth factor ( PDGF )	The change value of serum level of platelet growth factor ( PDGF ) will be compared with baseline.	during baseline to 6months after therapy
The change value of Birmingham Vasculitis Activity Score (BVAS)	The investigator will record the score. The BVAS is the most effective validated tool to document disease activity, ranging from 0 to 63. A score greater than or equal to 15 indicates that the disease is active. The higher score means the higher disease activity and a worse outcome.	during baseline to 6months after therapy
The change value of the Indian Takayasu Clinical Activity Score (ITAS) 2010	The investigator will record the score. ITAS 2010, a useful measure of clinical disease activity, ranges from 0 to 51 points. A score greater than or equal to 2 indicates that the disease is active. The higher score means the higher disease activity and the worse outcome.	during baseline to 6months after therapy
The change value of the Vasculitis Damage Index (VDI)	Disease damage will be evaluated using the Vasculitis Damage Index (VDI). It ranges from 0 to 64 points. The higher score means the more severe vascular damage and the worse outcome.	during baseline to 6months after therapy
The change value of the number of affected blood vessels	The number of affected blood vessels will be performed by Doppler US, CT angiography, magnetic resonance angiography (MRA), or digital subtraction angiography. The change value of the number will be compared with baseline.	during baseline to 6months after therapy
Rate of the usage of glucocorticoids	The investigator will observe and record the usage of glucocorticoids.	during baseline to 6months after therapy

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Principal Investigator: Yi Zhao, MD, Xuanwu Hospital, Capital Medical University, China, 10053; Principal Investigator: Sijie Li, MD, Xuanwu Hospital, Capital Medical University, China, 10053

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): December 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: remote ischemic conditioning; Takayasu Arteritis; Cerebral Ischemia
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Vasculitis; Skin Diseases, Vascular; Infarction; Stroke; Brain Infarction; Aortic Diseases; Brain Ischemia; Ischemia; Cerebral Infarction; Arteritis; Takayasu Arteritis; Aortic Arch Syndromes
• Other Study ID Numbers: TARIC-1

Drug and device information, study documents

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