Clinical trial NCT05342714: Remote Ischemic Conditioning for Chronic Cerebral Artery Occlusion
Official title: Safety and Efficacy of Remote Ischemic Conditioning in Patients With Chronic Cerebral Artery Occlusion: A Prospective, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cerebral Artery Occlusion
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2022-04-25
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic cerebral artery occlusion (CCAO), which is characterized by the pathophysiological change of long-term cerebral hemodynamic disorder, is one of the major risk factors affect the occurrence and recurrence of ischemic stroke. However, the mechanism of CCAO injury is not clear and effective treatment is warranted. The purpose of this study is to investigate the protective effect and underlying mechanism of remote ischemic conditioning (RIC) on CCAO.

Detailed description: CCAO is a cerebrovascular disease due to cerebral hypo-perfusion. It is often associated with repeated ischemic stroke or transient neurological symptoms, progressive cognitive decline and reduction of daily ability. Specific and effective treatment is warranted for symptomatic management of CCAO. RIC 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 symptomatic intracranial arterial stenosis in cerebral blood flow and metabolism. RIC can also ameliorate cerebral small vessel disease in slowing cognition decline and reducing white matter. Therefore, it is worth to investigate the neuroprotective mechanism of RIC for CCAO.

Eligibility criteria: Inclusion Criteria:

* (1) Age range 40-80 years, regardless of gender;
* (2) Digital angiography (DSA) / ultrasound / CT angiography (CTA) / magnetic resonance angiography (MRA) showed unilateral internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion and stenosis of any other cerebral arteries (e.g. the other side of ICA or MCA, basilar artery) \< 50%;
* (3) Modified Rankin Scale (mRS) score 0-2;
* (4) Symptoms of ischemic cerebrovascular disease (ischemic stroke or TIA) due to ICA or MCA occlusions within 12 months prior to enrollment;
* (5) neurological deficits were stable ≥ 30 days after occlusion;
* (6) Magnetic resonance perfusion weighted imaging (PWI) showed mean transit time (MTT) ≥ 4s and related cerebral blood flow (rCBF) (symptomatic side/asymptomatic side) \< 0.95;
* (7) The subject or its legally authorized representative is able to provide informed reports.

Exclusion Criteria:

* (1) Uncontrolled hypertension despite the use of antihypertensive drugs before enrollment (defined as systolic blood pressure ≥200mmHg);
* (2) Stenosis or occlusion of subclavian artery and upper limb artery;
* (3) Previous history of cerebral hemorrhage, including intracranial hemorrhage, ischemic stroke hemorrhage transformation, vascular malformation or intracranial tumor or other parts of the active bleeding disease;
* (4) History of brain tumor or mental illness or acute stroke ≤6 months;
* (5) Suffering from cardiogenic thrombosis diseases, such as mitral stenosis and atrial fibrillation, myocardial infarction, mural thrombosis or valvular vegetations, congestive heart failure or endocarditis within six months;
* (6) Obvious disorder of coagulation mechanism;
* (7) Severe liver or kidney insufficiency, malignant tumor, or serious diseases requiring medical intervention or surgery;
* (8) There is soft tissue or blood vessel injury at the cuff compression site of RIC treatment, or other conditions that cannot tolerate RIC;
* (9) Pregnant or lactating women;
* (10) Life expectancy \<6 months;
* (11) Refusal to sign informed consent, poor compliance, or inability to complete complete treatment, etc.

Primary outcomes:
measure: Change of cerebral blood flow perfusion
timeFrame: 180 days
Secondary outcomes:
measure: Recurrence times of stroke or transient ischemic attack (TIA)
timeFrame: 180 days
measure: Changes of volume of WMHs
timeFrame: 180 days
measure: Change of the direction of white matter cellulose
timeFrame: 180 days
measure: Change of cerebral hemoglobin oxygenation status
timeFrame: 180 days
measure: Change of collateral circulation
timeFrame: 180 days
measure: Change of the Montreal Cognitive Assessment (MoCA) score
timeFrame: 180 days
measure: Change of the Verbal Fluency Test (VFT) score
timeFrame: 180 days
measure: Change of the Digit Span Forward and Backward score
timeFrame: 180 days
measure: Change of the Hamilton Depression-17 (HAMD-17) scale
timeFrame: 180 days
measure: Change of the Hamilton Anxiety (HAMA) scale
timeFrame: 180 days
measure: Adverse events related to RIC treatment
timeFrame: From baseline to 180-day treatment
Other outcomes:
measure: Safety of RIC [Number of patients not tolerating RIC procedure and patients with erythema or skin lesions related to RIC]
timeFrame: 180 days
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Xunming Ji, MD.PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012 Oct 30;79(18):1853-61. doi: 10.1212/WNL.0b013e318271f76a. Epub 2012 Oct 3.
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.