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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS062778-05
Application #
8499434
Study Section
Special Emphasis Panel (ZNS1-SRB-B (11))
Program Officer
Conwit, Robin
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$2,026,879
Indirect Cost
$261,401
Name
Emory University
Department
Emergency Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Dickert, Neal W; Mah, Victoria A; Biros, Michelle H et al. (2014) Consulting communities when patients cannot consent: a multicenter study of community consultation for research in emergency settings. Crit Care Med 42:272-80
Johnston, S Claiborne; Easton, J Donald; Farrant, Mary et al. (2013) Platelet-oriented inhibition in new TIA and minor ischemic stroke (POINT) trial: rationale and design. Int J Stroke 8:479-83
Yeatts, Sharon D (2013) Novel methodologic approaches to phase I, II, and III trials. Stroke 44:S116-8