Clinical trial NCT05207475: Safety and Efficacy of Remote Ischemic Conditioning on Cerebral Amyloid Angiopathy. (RIC-CAA)
Official title: Safety and Efficacy of Remote Ischemic Conditioning in Patients With Cerebral Amyloid Angiopathy: A Prospective, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cerebral Amyloid Angiopathy
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2022-01-26
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 (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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes of volume of WMHs.
timeFrame: From baseline to 6 months and 1 year treatment.
Secondary outcomes:
measure: Adverse events related to RIC treatment.
timeFrame: From baseline to 6 months and 1 year treatment.
measure: Incidence of cardio-cerebral vascular events.
timeFrame: From baseline to 6 months and 1 year treatment.
measure: Changes of the cerebral blood flow in MRI ASL.
timeFrame: From baseline to 6 months and 1 year treatment.
measure: Changes of cognition evaluation on MoCA.
timeFrame: From baseline to 6 months and 1 year treatment.
measure: Changes of cognition evaluation on TMT tests.
timeFrame: From baseline to 6 months and 1 year treatment.
measure: Changes of cognition evaluation on stroop tests.
timeFrame: From baseline to 6 months and 1 year treatment.
measure: Changes in evaluation of Timed-Up-and-Go tests.
timeFrame: From baseline to 6 months and 1 year treatment.
measure: Changes of the whole volume of microbleeds.
timeFrame: From baseline to 6 months and 1 year treatment.
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, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.