Remote Ischemic Conditioning for Cerebral Amyloid Angiopathy-related Intracerebral Hemorrhage

Study Overview
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Brief Summary
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Cerebral amyloid angiopathy-related intracerebral (CAAH) hemorrhage is second factor of primary intracerebral hemorrhage. However, no effective prevention and treatment strategies have been established. Remote ischemic conditioning is a neuroprotective strategy. In animal studies，RIC is efficiency in accelerating the absorption of hematoma. Therefore, the investigators plan to carry out this research to evaluate the safety and efficacy of RIC in patients with CAA related ICH.

Detailed Description
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In China, primary intracerebral hemorrhage accounts for 80-85% of all types of intracerebral hemorrhage, while cerebral amyloid angiopathy-related intracerebral hemorrhage is the second factor, accounting for approximately 20-30%. It is often characterized by repeated and multifocal lobar hemorrhage, which will not only cause neurological deficit on the limbs, but also influence the cognitive level of patients and may even be life-threatening. At present, the role of surgery in CAA-related ICH is controversial, and there is no effective prevention and treatment strategies have been established. Additionally, it is always associated with a low rate of good prognosis(11%-60%) and a high risk of recurrent ICH (10%-60%). Thus, a novel approach which can improve the clinical outcome and reduce the risk of recurrent intracerebral hemorrhage is urgently needed. Remote ischemic conditioning (RIC) has been developed as a neuroprotective strategy to prevent and treat acute ischemic stroke and small cerebrovascular disease. Additionally, clinical research testified that RIC is safe and feasible for patients with subarachnoid hemorrhage. In animal studies, RIC is efficiency in accelerating the absorption of hematoma. Therefore, the investigators plan to carry out this research to evaluate the safety and efficacy of RIC in patients with CAA related ICH.

Official Title
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Safety and Efficacy of Remote Ischemic Conditioning in Patients With Cerebral Amyloid Angiopathy-related Intracerebral Hemorrhage:A Multicenter, Randomized, Controlled Study

Conditions
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Intracerebral Hemorrhage Lobar, Cerebral Amyloid Angiopathy

Intervention / Treatment
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* Device: Remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥55 and ≤85. The diagnosis of single or multiple spontaneous lobar cerebral hemorrhage is confirmed by brain CT scan(defined as possible or probable CAA by the Boston criteria) . Hematoma volume of 10 to 50 ml. Glasgow Coma Score (GCS)>8. Without surgery. Starting RIC treatment between 24 and 48 hours of ictus. Signed and dated informed consented is obtained. Exclusion Criteria: Patients with suspected secondary ICH related to tumor, coagulopathy, ruptured aneurysm or arteriovenous malformation, or venous sinus thrombosis. ICH concomitant with intraventricular hemorrhage, subdural hematoma, epidural hematoma subarachnoid hemorrhage or the condition of unstable vital signs which may be life-threatening. Evidence of significant shift of midline brain structure (>5mm) or herniation on brain imaging. Contraindication to MRI scan, such as intracranial metal implants, cardiac pacemaker, severe claustrophobia, history of seizures and so on Patients with a pre-existing neurological deficits (modified Ranks scale score >2) or psychiatric disease that would confound the neurological or functional evaluations. Use of warfarin or heparin within 7 days before the baseline visit Contraindication for remote ischemic conditioning: severe soft tissue injury, limb deformities, fracture, atrial fibrillation or peripheral vascular disease in the upper limbs. Life expectancy of less than 1 year due to co-morbid conditions. Severe, sustained hypertension (SBP > 180 mmHg or DBP > 110 mmHg). Severe hepatic and renal dysfunction. Known pregnancy (or positive pregnancy test), or breast-feeding. Concurrent participation in another research protocol for investigation of another experimental therapy. Any condition which, in the judgment of the investigator, might increase the risk to the patient.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIC group<br>RIC treatment and regular treatment. | Device: Remote ischemic conditioning<br>* RIC is a non-invasive therapy that performed by an electric autocontrol 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 once daily for consecutive 10-14 days after enrollment.<br>|
| No Intervention: Regular treatment<br>Regular treatment alone. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events | Safety | 90±7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of intracerebral hematoma volume | Intracerebral hematoma volume (ml) is assessed by CT brain scan. | 14± 2 days | 
| Changes of perihematomal edema volume | Perihematomal edema volume (ml) is assessed by CT brain scan. | 14± 2 days | 
| Incidence rate of the perihematomal edema expansion | The enlargement of perihematomal edema volume (ml) is assessed by CT brain scan. | 14± 2 days | 
| Shift of midline brain structure | Shift of midline brain structure (mm) is assessed by CT brain scan | 14± 2 days | 
| Prognosis of function outcome at 90 Days | accessed by modified Rankin score | 90±7 days | 
| Prognosis of neurological function at 90 Days | The Barthel index will be assessed at follow-up. | 90±7 days | 
| Changes of serum biomarker of blood brain barrier (Matrix metalloproteinases，MMPs) | The biomarker of blood brain barrier（MMPs） are assemented by the same laboratory. | 7± 2 days | 
| Changes of serum biomarker of inflammatory ( interleukin) | The interleukin will be assemented by the same laboratory. | 7± 2 days | 
| Other adverse events related to RIC treatment | Other adverse events related to RIC treatment,such as mucocutaneous hemorrhage,changes in coagulation function and so on. | 90±7 days |