Characterization of Circulating Extracellular Vesicles/Exosomes as New Predictive Biomarkers in Stroke Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 88
- 试验地点
- 2
- 主要终点
- Change in modified Barthel index after rehabilitation
研究概览
简要总结
The combination of rehabilitation protocols and regenerative therapies offers the outstanding opportunity to promote and enhance the endogenous regenerative and repair processes occurring in tissues damaged or lost due to injury, disease, or age. Still, one of the main hurdles in the clinical approach to regenerative rehabilitation is the lack of easily accessible and sensitive biomarkers for the evaluation of rehabilitation and therapy efficacy. Extracellular vesicles (EVs) are nanoscaled vesicles that mediate intercellular communication among organs. EVs were shown to be involved in the onset, progression and resolution of many disorders, being also used as valuable tool in the regenerative medicine field. However, the initial enthusiastic approach to EVs has been hindered in its transfer to clinics because of technological obstacles related to their dimensions and to their limited amount. The present project proposes the application of a Surface Plasmon Resonance imaging (SPRi)-based biosensor for the detection and characterization of blood EVs from stroke patients, before and after rehabilitation. After the successful SPRi detection of EVs of different cellular origin (brain and non-brain cells), the quantification of specific surface molecules related to pathological or regeneration processes will be accomplished. 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 in their cargo during disease progression and rehabilitation induced recovery, 2) provide support for using the proposed SPRi-based biosensor for the detection and characterization of circulating EVs in order to evaluate the efficacy of rehabilitation protocols and regenerative therapies, 3) identify new biomarkers for the profiling of stroke patients to personalize the rehabilitation therapies.
详细描述
OBJECTIVE: The aim of the project will be the evaluation of the prognostic power of circulating extracellular vesicles (EVs) in the serum of stroke patients. The characterization by SPRi of different families of EVs will allow to evaluate the activation status of the processes of neuroinflammation, neuronal regeneration, angiogenesis and cellular damage to provide a picture of the mechanisms of response to the damage taking place in the patient. These data will be correlated with emerging prognostic markers derived from the literature (Gandolfi et al, 2017) and with the outcome of the rehabilitation evaluated with specific functional and neurological scales that allow accurate profiling of the patient and the evaluation of functional recovery, according to what recently validated in the "Minimum rehabilitation evaluation protocol of the person with Cerebral Stroke Version 2020 - PMIC 2020" by the Italian Society of Physical and Rehabilitative Medicine (SIMFER) (https://springerhealthcare.it/mr/numero/volume-34-n- 2-June-2020 /).
The PMIC 2020 aims to provide each physiatrist / Rehabilitation Team with a uniform tool for the assessment of the person with stroke in the different phases of the disease, from acute hospital to territorial rehabilitation.
Specific objectives will be:
i) optimization of the SPRi method for the identification of different families of EVs in the serum of healthy subjects; ii) evaluation of the feasibility of the SPRi based method for the characterization of EVs from the serum of stroke patients; iii) preliminary study of the correlation between SPRi data, soluble markers of inflammation and regeneration, patient profiling and rehabilitation outcome at discharge.
IMPACT: The personalization of the rehabilitation plan in relation to the injury suffered and the patient's active response would lead to an increased probability of functional recovery, with benefits in terms of quality of life for the patient and family members, and a reduction in the management costs of the for the National Health System.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of ischemic or haemorrhagic stroke related to intensive post-stroke rehabilitation hospitalization
- •within 15 days of the ictal event
排除标准
- •Previous head injuries/traumas
- •Oncological diseases
- •Diseases of the immune and haematological system
- •Neurodegenerative diseases
结局指标
主要结局
Change in modified Barthel index after rehabilitation
时间窗: 01/11/2020 - 30/03/2022
modified Barthel index (Shah et al., 1989)
次要结局
- Extracellular vesicles characterization by SPRi(25/06/2018 - 30/09/2022)
- Change in Trunk control test after rehabilitation(25/06/2018 - 30/09/2022)
- Change in Functional ambulation classification(25/06/2018 - 30/09/2022)
- Change in Addenbrooke's Cognitive Examination scale after rehabilitation(25/06/2018 - 30/09/2022)
- Change in Short Physical Performance Battery (SPPB) after rehabilitation(25/06/2018 - 30/09/2022)
- Change in Hospital Anxiety and Depression Scale (HADS) after rehabilitation(25/06/2018 - 30/09/2022)
- Change in Fugl-Meyer Assessment (FMA) scale after rehabilitation(25/06/2018 - 30/09/2022)
- Change in Numeric Rating Scale (NRS) PAIN or PAINAD for non-verbal patient after rehabilitation(25/06/2018 - 30/09/2022)
- Change in anamnestic and current modified RANKIN scale after rehabilitation(25/06/2018 - 30/09/2022)
- Change in NIH-STROKE SCALE after rehabilitation(25/06/2018 - 30/09/2022)
- Change in Cumulative illness rating scale (CIRS) after rehabilitation(25/06/2018 - 30/09/2022)