Safety and Efficacy of Remote Ischemic Conditioning on Cerebral Amyloid Angiopathy. (RIC-CAA)

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Cerebral Amyloid Angiopathy: A Prospective, Randomized, Controlled Study

Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease, characterized by symptomatic intracerebral hemorrhage and cognitive impairment. However, no effective prevention and treatment strategies have been established. This study aims to evaluate the safety and efficacy of remote ischemic conditioning on patients with CAA.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Amyloid Angiopathy
• Intervention / Treatment: Device: Remote ischemic conditioning

Detailed Description

CAA is a cerebrovascular disease caused by the deposition of β-amyloid in the walls of arteries, arterioles, and capillaries in the cerebral cortex and overlying leptomeninges. It is often associated with repeated lobar intracerebral hemorrhages, progressive cognitive decline, transient neurological symptoms and gait disturbances. No treatment is specific for symptomatic management of CAA up to date. Remote ischemic conditioning 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 cerebral small-vessel disease in slowing cognition decline and reducing white matter hyperintensities. Thereby, investigators design this study to assess whether RIC has a beneficial effect on CAA.

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

Contacts and Locations

• Study Contact: Name: Xunming Ji, MD PhD; Phone Number: 010-83199430; Email: jixm@ccmu.edu.cn
• Study Contact Backup: Name: Mengke Zhang, MD; Email: zwzmk985@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100069
      • Recruiting
      • Xuan Wu Hospital，Capital Medical University
      • Contact: xunming ji; Phone Number: 861013120136877; Email: jixunming@vip.163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age≥55 and ≤85.
2. The diagnosis of probable CAA and probable CAA with supporting pathology by the Boston criteria.
3. Signed and dated informed consented is obtained.

Exclusion Criteria:

1. Familial hereditary CAA or other hereditary small-vessel disorders.
2. Previous intracranial hemorrhage caused by other reasons, such as tumor, cerebral cavernous angioma, ruptured aneurysm, arteriovenous malformation, venous sinus thrombosis and so on.
3. A history of stroke within 3 months.
4. The degree of intracranial or extracranial large artery stenosis >50%.
5. Clinical diagnosis of probable AD by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
6. Significant cognitive impairment (defined as Mini-mental State Examination (MMSE) score of ≥20 (primary school) or ≥24 (junior school or above) or other diseases resulting from severe cognitive impairment.
7. Inability to walk 6m unaided or other conditions that affected gait performance, such as Parkinson.
8. Illiteracy and patients with severe visual or hearing impairment.
9. Contraindication to MRI scan, such as intracranial metal implants, cardiac pacemaker, severe claustrophobia, history of seizures and so on.
10. Patients with missing or poor-quality MRI sequences at baseline and follow-up.
11. Patients with a pre-existing neurological deficits (modified Ranks scale score >2) or psychiatric disease that would confound the neurological or functional evaluations.
12. Alcohol dependence and other psychoactive substance abuse
13. Contraindication for remote ischemic conditioning: severe soft tissue injury, limb deformities, fracture, atrial fibrillation or peripheral vascular disease in the upper limbs.
14. Life expectancy of less than 1 year due to co-morbid conditions.
15. Severe, sustained hypertension (SBP > 180 mmHg or DBP > 110 mmHg).
16. Severe renal or hepatic disease.
17. Known pregnancy (or positive pregnancy test), or breast-feeding.
18. Concurrent participation in another research protocol for investigation of another experimental therapy.
19. Any condition which, in the judgment of the investigator, might increase the risk to the patient.

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; RIC treatment and regular treatment.	Device: Remote ischemic conditioning; RIC is a non-invasive therapy that performed by an electric auto-control device with cuff placed on arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuff on one arm. The procedure will be performed twice daily for consecutive 1 years after enrollment.
No Intervention: Regular treatment; Regular treatment alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of volume of WMHs.	The volume of WMHs was measured on Flairs at 6months and 12months.	From baseline to 6 months and 1 year treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 6 months and 1 year treatment.
Incidence of cardio-cerebral vascular events.	Incidence of cardiovascular and cerebrovascular events,such as Intracranial hemorrhage, subarachnoid hemorrhage, CAA-related transient focal neurological episodes（CAA-TFNEs）, CAA-related Inflammation（CAA-ri），ischemic stroke during follow-up.	From baseline to 6 months and 1 year treatment.
Changes of the cerebral blood flow in MRI ASL.	Changes of the CBF are assessed by Arterial Spin Labeling (ASL) MRI techniques at 6months and 12months.	From baseline to 6 months and 1 year treatment.
Changes of cognition evaluation on MoCA.	We used MoCA to evaluate the cognitive functions,of subjects at 6months and 12months, such as memory, execution, visuospatial function and so on.	From baseline to 6 months and 1 year treatment.
Changes of cognition evaluation on TMT tests.	We used TMT tests to evaluate execution and and so on at 6months and 12months.	From baseline to 6 months and 1 year treatment.
Changes of cognition evaluation on stroop tests.	We used stroop tests to evaluate execution and and so on at 6months and 12months.	From baseline to 6 months and 1 year treatment.
Changes in evaluation of Timed-Up-and-Go tests.	We used Timed-Up-and-Go tests to evaluate the gait function of subjects at 6months and 12months.	From baseline to 6 months and 1 year treatment.
Changes of the whole volume of microbleeds.	The volume of microbleeds was measured on QSM at 6months and 12months.	From baseline to 6 months and 1 year treatment.

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Principal Investigator: Xunming Ji, MD PhD, Xuanwu Hospital, Beijing

Publications and helpful links

General Publications

• 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.
• Chen SJ, Tsai HH, Tsai LK, Tang SC, Lee BC, Liu HM, Yen RF, Jeng JS. Advances in cerebral amyloid angiopathy imaging. Ther Adv Neurol Disord. 2019 May 3;12:1756286419844113. doi: 10.1177/1756286419844113. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 20, 2022
• Primary Completion (Anticipated): January 20, 2022
• Study Completion (Anticipated): January 20, 2022

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: January 12, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: January 12, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Proteostasis Deficiencies; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Cerebral Small Vessel Diseases; Amyloidosis, Familial; Amyloidosis; Cerebral Amyloid Angiopathy; Cerebral Amyloid Angiopathy, Familial
• Other Study ID Numbers: RIC-CAA

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