Clinical trial NCT04757597: Remote Ischemic Conditioning for Cerebral Amyloid Angiopathy-related Intracerebral Hemorrhage
Official title: Safety and Efficacy of Remote Ischemic Conditioning in Patients With Cerebral Amyloid Angiopathy-related Intracerebral Hemorrhage:A Multicenter, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Intracerebral Hemorrhage Lobar
Cerebral Amyloid Angiopathy
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Wangjing Hospital, China Academy of Chinese Medical Sciences
name: Bejing Fengtai You'anmen Hospital
First posted: 2021-02-17
Enrollment: 30
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: 90±7 days
Secondary outcomes:
measure: Changes of intracerebral hematoma volume
timeFrame: 14± 2 days
measure: Changes of perihematomal edema volume
timeFrame: 14± 2 days
measure: Incidence rate of the perihematomal edema expansion
timeFrame: 14± 2 days
measure: Shift of midline brain structure
timeFrame: 14± 2 days
measure: Prognosis of function outcome at 90 Days
timeFrame: 90±7 days
measure: Prognosis of neurological function at 90 Days
timeFrame: 90±7 days
measure: Changes of serum biomarker of blood brain barrier (Matrix metalloproteinases，MMPs)
timeFrame: 7± 2 days
measure: Changes of serum biomarker of inflammatory ( interleukin)
timeFrame: 7± 2 days
measure: Other adverse events related to RIC treatment
timeFrame: 90±7 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuan Wu Hospital，Capital Medical University
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Xunming Ji
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yamada M. Cerebral amyloid angiopathy: emerging concepts. J Stroke. 2015 Jan;17(1):17-30. doi: 10.5853/jos.2015.17.1.17. Epub 2015 Jan 30.
citation: Arima H, Tzourio C, Anderson C, Woodward M, Bousser MG, MacMahon S, Neal B, Chalmers J; PROGRESS Collaborative Group. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke. 2010 Feb;41(2):394-6. doi: 10.1161/STROKEAHA.109.563932. Epub 2009 Dec 31.