Minocycline to Improve Neurologic Outcome (MINO Clinical Trial)

米诺环素改善神经系统结果（MINO 临床试验）

基本信息

批准号：
7265406
负责人：
DAVID C. HESS
金额：
$ 57.51万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7265406
关键词：
Acute African American Alteplase Ambulances Amyotrophic Lateral Sclerosis Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antibiotics Apoptotic Basic Science Blood - brain barrier anatomy Cell Death Cells Cerebral Ischemia Cerebral hemisphere hemorrhage Clinical Clinical Trials Clinical Trials Network Cultured Cells Data Development Dose Drug Kinetics Endopeptidases Enrollment Future Hospitals Hour Human Huntington Disease In Vitro Industry Infarction Inflammation Inflammatory Response Intervention Intracranial Hemorrhages Intravenous Investigation Ischemia Ischemic Stroke Kentucky Label Laboratories Matrix Metalloproteinases Maximum Tolerated Dose Mechanics Medical Methods Middle Cerebral Artery Occlusion Minocycline Modeling Multiple Sclerosis Neurological Models Neurological emergencies Neurological outcome Neuroprotective Agents Numbers Outcome Parkinson Disease Patients Penetration Peptide Hydrolases Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Plasma Population Property Protease Inhibitor Qualifying Randomized Research Research Personnel Risk Risk Factors Rodent Model Route Rural Community Rural Hospitals Safety Scientist Serum Statistical Methods Stroke System Testing Therapeutic Thrombolytic Therapy Time Translating USA Georgia United States Food and Drug Administration Universities Western Asia Georgia college day design experience functional outcomes improved in vivo inhibitor/antagonist interest nervous system disorder neuroprotection novel prevent programs size stroke therapy tissue culture

项目摘要

DESCRIPTION (provided by applicant): Minocycline is a safe and well-tolerated antibiotic with excellent blood-brain barrier penetration. Recent evidence demonstrates that minocycline is a promising neuroprotective agent and is effective in animal models of global and focal ischemia. Minocycline has anti-inflammatory and anti-apoptotic effects and also inhibits the matrix metalloproteinases. Moreover, minocycline is neuroprotective in a rodent model of temporary focal ischemia at serum concentrations that are likely to be achievable in humans. Minocycline is presently in clinical trial in Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. This proposal is a phase Ib/lla clinical trial of minocycline in acute ischemic stroke. The central hypothesis is that minocycline will be safe and tolerable in acute ischemic stroke patients when administered in a dose, route, and time window associated with neuroprotection in animal models. We plan to test our central hypothesis and accomplish the overall objective of this application by performing a dose-finding study using an open label, non-randomized, dose escalation design with a novel statistical method for stroke trials, the modified continual reassessment method. The specific aims are: 1.) Determine the maximally tolerated dose (MTD) of intravenous minocycline in patients with acute ischemic stroke. 2.) Determine the pharmacokinetics of minocycline in patients with ischemic stroke 3.) Determine the effect of different doses of minocycline on plasma MMP-9 activity 4.) Gather preliminary data of the effect of different doses of minocycline on functional outcome This proposal will generate data that is critical to the development of a later phase ll/lll study of minocycline in acute ischemic stroke. There is a desperate need for a safe and effective neuroprotective agent that could be given to a diverse group of stroke patients. Since it is a safe drug and may also have activity against intracerebral hemorrhage, minocycline has excellent potential to become a "field drug", administered by ambulance crews and in rural hospitals.

描述（由申请人提供）：米诺环素是一种安全且耐受良好的抗生素，具有出色的血脑屏障穿透。最近的证据表明，米诺环素是一种有前途的神经保护剂，在全球和局灶性缺血动物模型中有效。米诺环素具有抗炎和抗凋亡作用，也抑制基质金属蛋白酶。此外，在人类中可能可以实现的血清浓度下，米诺环素在临时局灶性缺血的啮齿动物模型中具有神经保护作用。米诺环素目前正在帕金森氏病，肌萎缩性侧索硬化症，亨廷顿氏病和多发性硬化症的临床试验中。该提案是急性缺血性中风中米诺环素的IB/LLA期临床试验。中心假设是，在动物模型中与神经保护相关的剂量，途径和时间窗口时，急性缺血性中风患者的米诺环素将是安全可耐受的。我们计划通过使用开放标签，非随机剂量升级设计进行剂量调查研究来测试我们的中心假设，并实现该应用的整体目标，并使用用于中风试验的新型统计方法，这是修改的持续重新评估方法。具体目的是：1。）确定急性缺血性中风患者静脉内米诺环素的最大耐受剂量（MTD）。 2.) Determine the pharmacokinetics of minocycline in patients with ischemic stroke 3.) Determine the effect of different doses of minocycline on plasma MMP-9 activity 4.) Gather preliminary data of the effect of different doses of minocycline on functional outcome This proposal will generate data that is critical to the development of a later phase ll/lll study of minocycline in acute ischemic stroke.迫切需要一种安全有效的神经保护剂，可以给予一群中风患者。由于它是一种安全的药物，也可能具有针对脑出血的活性，因此米诺环素有很大的潜力成为救护人员和农村医院管理的“现场药物”。