The objectives of this project are to demonstrate that 1) intravenous magnesium is beneficial in acute ischemic stroke as evidenced by decrease in the growth of infarct volume over time as measured by diffusion weighted magnetic resonance imaging (DWI); 2) DWI is a valuable surrogate outcome measure in acute ischemic stroke clinical trials; 3) diffusion/perfusion mismatch is a useful entry criterion for neuroprotective treatment in acute stroke clinical trials; and 4) intravenous magnesium is safe and potentially beneficial in intracerebral hemorrhage. During the first phase of the project, objectives 1-3 will be assessed by conducting a randomized, double-blind, placebo controlled trial to evaluate the efficacy of intravenous magnesium as a neuroprotective agent in acute ischemic stroke. The trial will use diffusion/perfusion magnetic resonance imaging as a surrogate outcome marker. 150 patients will be enrolled within 12 hours of symptom onset at 3 UCLA-associated hospitals. The second phase of this project will be a parallel pilot randomized, double-blind, placebo-controlled trial to evaluate the safety and explore the efficacy of intravenous magnesium in acute intracerebral hemorrhage, enrolling 40 patients. Additional data will be collected to assess the diffusion/perfusion MR signature of acute intracerebral hemorrhage. The findings of this project will have direct relevance to future treatment of acute ischemic and hemorrhagic stroke as well as to the design of future trials of neuroprotective agents. The results will help establish the utility of novel diffusion/perfusion MR techniques as demonstrating physiologic, objective changes that can be used as entry and outcome criteria in evaluating stroke patients. During the award period, in addition to serving as the principal investigator of these trials, Dr. Kidwell will pursue in-depth didactic multidisciplinary training in biostatistics, epidemiology, clinimetrics and magnetic resonance radiology. She will be mentored by Drs. Jeffrey Saver, Sidney Starkman, Jeffry Alger, and Barbara Vickrey. At the completion of this training, Dr. Kidwell will have acquired all requisite experience and skills to function as an independent investigator in clinical studies of novel magnetic resonance stroke imaging techniques, pivotal trials of promising therapeutic agents, and studies of the pathophysiology of acute human cerebral ischemia.
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