Traumatic brain injury (TBI) is a major cause of premature death and disability worldwide. No therapy has been effective in reducing mortality and improving functional outcomes. We recently completed an NINDS-funded, Phase I/IIa double-blinded, randomized placebo-controlled pilot clinical trial examining the pharmacokinetics, safety, and activity of progesterone, a steroid found to have powerful neuroprotective properties in multiple different animal models of brain injury. Based on the extensive preclinical evidence of activity and the promising findings of our pilot study we propose to conduct a phase III clinical trial to definitively assess the efficacy of this treatment for adults with moderate to severe acute TBI. Our primary objective is to determine the effect of administering intravenous progesterone (initiated within 4 hours of injury and administered for 72 hours, followed by an additional 24 hour taper) versus placebo for treating victims of moderate to severe (GCS 12-4) TBI. Our secondary objectives are to examine the effects of progesterone vs. placebo in patients with moderate to severe TBI on 6 month mortality, Disability Rating Scale score, cognitive, neurological and functional outcome using a select battery of tests, and the rates of adverse and severe adverse events. If the therapeutic benefits observed in animals and from our pilot study are replicated, administration of intravenous progesterone should decrease mortality and improve neurological function. Positive results would represent a major advance in the treatment of TBI.
Traumatic brain injury (TBI) is a major cause of premature death and disability worldwide, but no therapy to date has reduced mortality or improved functional outcomes. We recently completed an NINDS-funded, Phase IIa pilot clinical trial of progesterone, a steroid found to have powerful neuroprotective properties in multiple animal models of brain injury, for the treatment of acute TBI and found encouraging results. If the therapeutic benefits observed in animals and our pilot clinical trial are confirmed, it will represent a major advance in the treatment of TBI.
|Whitesides, Louisa W; Baren, Jill M; Biros, Michelle H et al. (2017) Impact of individual clinical outcomes on trial participants' perspectives on enrollment in emergency research without consent. Clin Trials 14:180-186|
|Fehr, Alexandra E; Scicluna, Victoria M; Pentz, Rebecca D et al. (2017) Patient and Surrogate Views of Community Consultation for Emergency Research. Acad Emerg Med 24:1410-1414|
|Denninghoff, Kurt R; Nuño, Tomas; Pauls, Qi et al. (2017) Prehospital Intubation is Associated with Favorable Outcomes and Lower Mortality in ProTECT III. Prehosp Emerg Care 21:539-544|
|Goldstein, Felicia C; Caveney, Angela F; Hertzberg, Vicki S et al. (2017) Very Early Administration of Progesterone Does Not Improve Neuropsychological Outcomes in Subjects with Moderate to Severe Traumatic Brain Injury. J Neurotrauma 34:115-120|
|Scicluna, Victoria M; Ali, Mohammed K; Pentz, Rebecca D et al. (2017) Does experience matter? Implications for community consultation for research in emergency settings. AJOB Empir Bioeth 8:75-81|
|Sribnick, Eric Anthony; Shi, Junxin; Lunney, Michael P et al. (2016) 379?Communicating a Traumatic Brain Injury Patient's Potential Need for Operative Intervention: The Surgical Intervention for Traumatic Injury Scale. Neurosurgery 63 Suppl 1:213|
|Dickert, Neal W; Brown, Jeremy; Cairns, Charles B et al. (2016) Confronting Ethical and Regulatory Challenges of Emergency Care Research With Conscious Patients. Ann Emerg Med 67:538-45|
|Zhao, Wenle; Pauls, Keith (2016) Architecture design of a generic centralized adjudication module integrated in a web-based clinical trial management system. Clin Trials 13:223-33|
|Dickert, Neal W; Scicluna, Victoria M; Baren, Jill M et al. (2015) Patients' perspectives of enrollment in research without consent: the patients' experiences in emergency research-progesterone for the treatment of traumatic brain injury study. Crit Care Med 43:603-12|
|Wright, David W; Yeatts, Sharon D; Silbergleit, Robert (2015) Progesterone in traumatic brain injury. N Engl J Med 372:1766-7|
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