Remote Ischemic Conditioning: A collateral therapeutic and neuroprotectant

远程缺血调理：并行治疗和神经保护剂

基本信息

批准号：
10221786
负责人：
DAVID C. HESS
金额：
$ 49.27万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10221786
关键词：
Accident and Emergency department Acute Acute myocardial infarction Adult Alteplase Ambulances Animals Autologous Bilateral Blood Pressure Blood flow Brain Brain Ischemia Carotid Stenosis Cerebral hemisphere hemorrhage Cerebrovascular Circulation Cerebrum Clinical Clinical Trials Coagulation Process Denmark Development Disabled Persons Dose FDA approved Female Helicopter Hematoma Hospitals Infarction Injury Intervention Ischemic Stroke Left Limb structure Methodology Methods Middle Cerebral Artery Occlusion Minocycline Modeling Mus Neuroprotective Agents Outcome Pathway interactions Patients Pharmaceutical Preparations Phase Phase II Clinical Trials Procedures Randomized Randomized Controlled Trials Regimen Rehabilitation therapy Reperfusion Therapy Resolution Rest Rodent Safety Sample Size Stroke Testing Therapeutic Time Tissues Work acute stroke angiogenesis arm base bench to bedside data sharing design early phase clinical trial effective intervention effective therapy endovascular thrombectomy experience functional outcomes good laboratory practice improved improved outcome ischemic conditioning neuroprotection novel therapeutics operation outcome prediction pre-clinical preclinical study preconditioning response safety and feasibility stem cells stroke clinical trials stroke model stroke therapy stroke trials targeted treatment thrombolysis trial design

项目摘要

Thrombolysis and endovascular thrombectomy (ET), remain the only two FDA-approved ischemic stroke therapies. Despite the efficacy of ET, 50% of the patients remain disabled at 3 months. Adjunctive therapies to thrombolysis and ET are needed that provide “bridging neuroprotection” and improve collateral blood flow. Since presence of collaterals is a major predictor of outcome with ET, a promising new therapeutic avenue is development of “collateral therapeutics.” Remote ischemic conditioning (RIC), the simple and safe repetitive inflation-deflation of a blood pressure (BP) cuff on the limb, reduces infarct size, improves functional outcome, and improves cerebral and collateral blood flow in acute stroke. RIC can be administered in the ambulance, the helicopter, the Emergency Department, in the interventional suite, and in the hospital or rehabilitation facility and is therefore an ideal adjunctive treatment to ET. Our overall hypothesis is that RIC is an inexpensive, versatile, safe and effective therapy alone and in combination with tPA./ET in acute stroke. Our aims include: Aim 1: Working with the Coordinating Center and the Steering Committee, develop standard operation procedures, choice of stroke model, methods of randomization and blinding, sample size estimation and methods of data sharing Aim 2: Compare RIC and 5 other agents/interventions at optimal dosing regimens as adjunctive therapies to reperfusion in rodent acute stroke models in a pre-clinical multicenter randomized controlled trial (pRCT) design and advance the most effective intervention into phase II clinical trial.

溶栓和血管内血栓切除术（ET）仍然是仅有的两种FDA批准的缺血性中风疗法。尽管ET的效率是ET的效率，但有50％的患者在3个月时仍残疾。需要对溶栓和ET进行辅助疗法，以提供“桥接神经保护”并改善附带血流。由于抵押品的存在是ET结果的主要预测指标，因此有希望的新的治疗途径是“抵押疗法”的发展。远程缺血性调节（RIC），肢体上血压（BP）袖口的简单，安全重复通货膨胀，减少了梗塞大小，改善功能性预后，并改善急性中风中的脑和附加血流。 RIC可以在救护车，直升机，急诊科，介入套房，医院或康复设施中进行管理，因此是ET的理想辅助治疗方法。我们的总体假设是RIC是一种廉价，多功能，安全有效的治疗，并与急性中风中的TPA./ET结合使用。 Our aims include: Aim 1: Working with the Coordinating Center and the Steering Committee, developing standard operation procedures, choice of stroke model, methods of randomisation and blinding, sample size estimation and methods of data sharing Aim 2: Compare RIC and 5 other agents/interventions at optimal dosing regimens as Adjunctive therapies to reperfusion in rodent acute stroke models in a pre-clinical multicenter randomized controlled trial (pRCT)设计并将最有效的干预措施纳入II期临床试验。