Rheo-Erythrocrine Dysfunction as a Biomarker for RIC Treatment in Acute Ischemic Stroke - Pilot, Single-center, Randomized, Patient-assessor Blinded, Sham-controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- RBC deformability will serve as a biomarker of the conditioning response and predictor of the clinical outcome in stroke patients.
研究概览
简要总结
This study aims to investigate whether Remote Ischemic Conditioning (RIC) improves rheo-erythrocrine dysfunction in acute ischemic stroke
详细描述
Stroke is a leading cause of death and disability worldwide. Of all strokes, 85% are ischemic strokes caused by a thrombus or an embolus. The additional 15% are caused by hemorrhage. Currently the only approved treatments for ischemic strokes are thrombolysis given within 4.5 hours and thrombectomy performed within 6 hours of symptom onset - in some cases up to 24 hours. The majority of stroke patients are not however eligible for acute reperfusion therapy, mainly due to time constrains and late presentation. Novel neuroprotective strategies available for all stroke patients are thus urgently needed.
Remote Ischemic Conditioning (RIC) is a simple intervention in which transient ischemia is induced in an extremity by repetitive inflation-deflation of a blood pressure cuff. It remains uncertain exactly how the protective effect of RIC is transmitted and communicated between the extremity and the brain. Both humoral, immunological and neuronal pathways seem to be involved. Treatment with RIC and has proven to be a safe, feasible and low-cost treatment in clinical settings.
Biomarkers of the RIC treatment is a new area of stroke research and are important to establish in order to assess and predict responders of the conditioning treatment. Rheo-erythrocrine dysfunction of the Red Blood Cell (RBC) is a novel biomarker in both ischemic strokes in general and on the effect of RIC. Red Blood Cells with a diameter of 6-8 μm must be highly deformable in order to deliver oxygen to brain tissue by travelling through micro vessels with a diameter of just 2-3 μm. RBC's can carry nitric oxide as NO2-/s-nitrosylated proteins. These proteins improve RBC deformability and induce hypoxic vasodilation thereby improving passage through the microvasculature. RBC's also express Erythrocyte Nitric Oxide Synthase 3, which regulate the rheo-erythrocrine function. Erythrocyte Nitric Oxide Synthase 3 is activated by shear stress and provide an extra source of NO for hypoxic vasodilation. Preliminary data have shown that experimental stroke on mice seems to cause a rheo-erythrocrine dysfunction of the RBC's leading to a loss of deformability. The RBC's become rigid, which can lead to occlusion of micro vessels in the brain and further ischemic damage. Loss of deformability can be measured as a reduced Elongation Index (EI) by ektacytometry and may be attenuated by RIC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •STROKE PATIENTS
- •Inclusion Criteria:
- •Onset to randomization < 48 hours
- •Independent in daily living (mRS 0-2)
- •Legal competent
- •Ambulatory
- •Documented ischemic stroke on baseline MRI
排除标准
- •Prior stroke, dementia or other known neurological condition Pregnancy
- •Contraindications to MRI
- •Investigators discretion
- •Known upper extremity peripheral arterial stenosis Diabetes
- •Inclusion Criteria:
- •Independent in daily living (mRS 0-2) Ambulatory
- •Legal competent
- •Non vascular diagnosis (e.g. epilepsy, migraine etc.)
- •Exclusion Criteria
- •Prior stroke, dementia or other known neurological condition
- •Pregnancy
- •Contraindications to MRI
- •Investigators discretion
- •Known upper extremity peripheral arterial stenosis Diabetes
结局指标
主要结局
RBC deformability will serve as a biomarker of the conditioning response and predictor of the clinical outcome in stroke patients.
时间窗: 1 week
RBC deformability is measured as Deformability or Elongation Index (DI or EI, Rheoscan AnD-300, RheoMeditech, South Chorea). A higher EI at the optimum viscosity (300 Osmolality) indicates highly deformable RBCs indicative of better microcirculation, while a lower EI indicates rigid RBC's. Briefly, 6 µL of heparinized or EDTA treated fresh blood is mixed with 600-µL of polyvinylpyrrolidone (PVP) solution (300 Osm) and transferred to a disposable kit. The kit is placed inside the laser-assisted ectacytometer for automated read out, data and image collection as per the vendor's instructions.
RBC deformability will serve as a biomarker of the conditioning response and predictor of the clinical outcome in stroke patients
时间窗: 1 week
For measurement of shear stress, 0,5 mL of heparinized or EDTA treated fresh blood is mixed with 600-µL of polyvinylpyrrolidone (PVP) solution (300 Osm) and transferred to a disposable kit. The kit is placed inside the laser-assisted ectacytometer for automated read out, data and image collection as per the vendor's instructions.
次要结局
- RBC deformability in relation to infarct size/stroke severity(1 week)
- RBC erythrocrine dysfunction (nitric) in relation to infarct size/stroke severity(9 months)
- RBC erythrocrine dysfunction (NOS3) presentation across stroke subtypes(9 months)
- RBC deformability presentation across stroke subtypes(1 week)
- RBC erythrocrine dysfunction (nitric oxide) presentation across stroke subtypes(9 months)
- Extracellular vesicle profile of RIC-induced neuroprotection(9 months)
- Nitric oxide quantification using DAF-FM-Diacetate flowcytometry as a biomarker of the conditioning response(1 week)
- Nitric oxide quantification using DAF-FM-Diacetate flowcytometry as a predictor of the short term clinical outcome in stroke patients(1 week)
- RBC erythrocrine dysfunction (NOS3) in relation to infarct size/stroke severity(9 months)
- Extracellular vesicle profile as a marker for RBC erythrocrine dysfunction and deformability(9 months)
- Difference in 7 days cognitive impairment between treatment groups(1 week)
- RBC erythrocrine dysfunction and deformability as a marker for difference in 7 days cognitive impairment (MoCA scale)(9 months)
- Circulating microRNA profile of RIC-induced neuroprotection(9 months)
- Circulating microRNA as a marker for difference in 7 days cognitive impairment (MoCA score)(9 months)
研究者
Grethe Andersen
Professor, DMSc, Senior Consultant, MD
Aarhus University Hospital