How and When Progesterone Is Administered After a Brain Injury
In the Phase III trial, humans are given natural progesterone — which comes from yams — within a four-hour window when it can coat the brain and offer neuro protection.
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The animal studies show that the neuro-protection works probably up to 12-- maybe even as much as 24--hours after injury. However, we--in our clinical trial and our phase three clinical trial now-- are required to get the drug in within 4 hours. The reason we're doing that is rather complex. The animal studies-- When you do an animal model, it's very homogenous. The brain injury is exactly the same. The animals are exactly the same. Everything is maintained equally. So, small improvements in outcome can be identified in an animal model. But when you go to a human model that is very heterogenous, that improvement can get washed out in the noise. From the animal studies we can show very clearly that the earlier you get it in the better it is. The 1-hour post, the 6-hour post, and the 12-hour post-- there's a scale that shows the earlier the better. It's common sense. It's a neuro-protectant--meaning it's got to protect-- so if you don't get it in early, you're already behind the eight ball. That was the reason in the phase three trial we chose a 4-hour window-- was to try to get it in absolutely as soon as possible but yet feasible, and give the drug maximal chance to work. The formulation that we use in the human trials is natural progesterone, so that's key. Many of the progestins--which are artificially produced progesterones-- have very different mechanisms and very different properties. So, it's natural progesterone which, by the way, comes from yams. We buy it as a powder from a company and dissolve it in a small amount of ethanol, and then it gets mixed into an intra-lipid formulation just before it's delivered. We give it as an IV infusion over 4 days with a taper towards the end. The goal is to reach a steady state--to sort of coat the brain-- during that critical time period immediately after the injury.
Posted on BrainLine October 25, 2012. Reviewed July 25, 2018.
Produced by Victoria Tilney McDonough, Ashley Gilleland, Justin Rhodes, and Erica Queen, BrainLine.
David Wright, MD is a tenured associate professor in the Department of Emergency Medicine, Emory University, and the director of the division of Emergency Neurosciences.