Evaluation of Predictive Circulating Biomarkers for Rehabilitation Recovery in Ischemic and Haemorrhagic Stroke Patients: from Lacunar Stroke to Vascular Severe Brain Injury
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Change in modified Barthel index after rehabilitation
研究概览
简要总结
The rehabilitation outcome and recovery, in people after stroke or with vascular severe brain injury(vSBI), are difficult to predict. Moreover, the clinical management of patients during hospitalization is problematic due to complex clinical conditions and complications, e.g. healthcare-associated infections(HAIs). Today we still lack early objective biomarkers that could predict the patient's trajectory at admission. Extracellular vesicles are nanoparticles naturally released by cells in physiological and pathological conditions. As important actors of cellular communication between different organs and body districts, EVs are currently under investigation as an informative tool able to reflect the clinical conditions of patients. Using an optimized Surface Plasmon Resonance imaging (SPRi) based biosensor, our main objective is to assess the predictive capacity of biomarkers associated to blood-derived extracellular vesicles for anticipating patients' recovery after stroke and vSBI. If successful, the project will 1) demonstrate the ability of the SPRi biosensor to reveal differences in the relative amount of specific cell-derived EV subpopulations and their molecular cargo during disease progression and rehabilitation-induced recovery, 2) verify the impact of HAI on patients' response, 3) perform a patient's stratification to personalize the rehabilitation protocol.
详细描述
OBJECTIVE: The main objective of the present project is to assess the predictive capacity of biomarkers associated to extracellular vesicles (EVs) for anticipating patients' recovery after stroke and vSBI.
The characterization by SPRi of different cell-derived families of EVs (endothelium, neurons, microglia, muscle, and neutrophil) will allow to evaluate the activation status of the processes of neuroinflammation, neuronal regeneration, and angiogenesis to provide a picture of the mechanisms of response to the damage taking place in the brain of patients and enhanced by the rehabilitation treatment. The selected markers are expected to be released in the brain, but they can be monitored in the periphery taking advantage of the ability of EVs to cross the blood-brain barrier.
Due to the weight of HAIs on patients' prognosis, inflammation and infections will represent the main covariate of the analysis in the search for predictive rehabilitation biomarkers.
Specific objectives are as follows:
- Evaluation of the SPRi biosensor's ability to detect EV-associated biomarkers correlating with stroke severity.
- Evaluation of the ability of EV-associated biomarkers to represent a recovery biomarker by their changes according to the patient's outcome.
- Evaluation of the ability of EV-associated biomarkers to identify infection-prone patients to help develop valuable prevention strategies for infections.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disability deriving from first ischemic or haemorrhagic stroke detected by MRI or CT scan
- •Time from stroke onset or rehabilitation admission less than 1 month (for stroke) 3 months (for vSBI)
- •Need of inward rehabilitation
- •Signed informed consent by patient or legal representative
排除标准
- •Subarachnoid haemorrhage
- •Cerebral venous thrombosis
- •Other previous neurological or psychiatric conditions
- •Autoimmune diseases
- •Previous severe and chronic infections conditions (e.g. tuberculosis, HIV/AIDS)
- •Neoplasms or other malignant conditions
- •Immunomodulatory medications (immunosuppressants).
结局指标
主要结局
Change in modified Barthel index after rehabilitation
时间窗: From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment)
Modified Barthel index (Shah et al., 1989) validated in the literature and already proposed in the PMIC 2020 and PMGCA 2020 by SIMFER, will be used for accurate patient profiling and assessment of functional recovery (for all groups).
次要结局
- Extracellular vesicles characterization by SPRi(From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment))
- Change in National Institute of Health Stroke Scale (NIHSS) (for stroke)(From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment))
- Change in Coma Recovery Scale (for vSBI)(From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment))
- Change in Level of Cognitive Functioning (LCF) (for vSBI)(From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment))
- Change in Glasgow Outcome Scale - Extended (GOSE) (for vSBI)(From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment))
- Change in Rehabilitation Complexity Scale (for all groups)(From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment))
- Change in Mini Mental State Evaluation (MMSE) (for stroke)(From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment))
- Change in Modified RANKIN scale (mRS) (for all groups)(From admission in the rehabilitation department (T0) to discharge (T2; max 2 months from enrollment))