Application

The use of progesterone to treat patients with traumatic brain injury (TBI) via a tapered administration protocol.

Key Benefits

• Early administration of progesterone reduces cerebral edema and neural loss, and improves behavioral recovery from traumatic brain injury (TBI) in pre-clinical animal models.
• Tapered progesterone withdrawal enhances recovery after TBI compared to acute withdrawal.
• Progesterone reduces mortality by 50% and improves functional outcomes in patients with TBI in phase II clinical trials.
• Tested in phase II and phase III clinical trials and has an acceptable safety profile.

Market Summary

Thousands of children under 18 are admitted and released from the hospital with an associated traumatic brain injury (TBI).  The majority of these hospitalized children are discharged with a permanent disability from a TBI. Currently only maintenance therapy is done for these patients, including monitoring and maintaining blood pressure, oxygenation and intracranial pressure, infection prophylaxis, and deep vein thrombosis prophylaxis. More than 30 clinical trials have investigated various compounds for the treatment of acute TBI, but no treatment has shown efficacy in these trials. There is still no effective pharmacotherapy for TBI.

Technical Summary

Progesterone has been shown to have various functions in neuroprotection, including inhibition of inflammatory cytokines, apoptosis reduction, excitotoxicity prevention, and control of vasogenic edema, in multiple animal models. Emory researchers have found that the use of progesterone to treat traumatic brain injury could improve outcomes for patients suffering from TBI. The inventors designed a method of progesterone administration via IV infusion with an initial high dose, several days of a lower dose, and then a tapered withdrawal. This method can allow quick drug delivery and achieve a constant and therapeutically effective serum concentration of progesterone. Administration of progesterone decreased mortality and improved functional outcomes in patients with TBI in two single-center clinical trials.

Development Stage

Failed to show efficacy in two randomized, double-blind, placebo-controlled phase III clinical trials, but may be effective in more homogeneous patient population following dose-optimization and duration of treatment in a more focused Phase 2B trial using more quantitative primary measures of functional outcomes.