Progesterone for the Treatment of Traumatic Brain Injury (ProTECT™ III) is a research study to see if progesterone, a hormone normally found in our bodies, is useful in limiting the amount of brain damage from traumatic brain injury (TBI). Many animal studies and two small studies in humans suggest that progesterone, given after TBI, may result in less brain damage.
The ProTECT III study will test whether progesterone along with standard medical care works better than standard medical care alone to limit damage from TBI in adults with moderate to severe TBI.
Progesterone is a potent steroid hormone that is naturally synthesized in the brain. In animal studies early administration of progesterone after experimental TBI reduces cerebral edema (brain swelling), neuronal loss, and limits behavioral deficits.
Certain properties of progesterone make it a better candidate for treatment compared to other drugs tested in the past. First, progesterone rapidly enters the brain and reaches equilibrium with the plasma within one hour of administration. Second, unlike other candidate agents, progesterone has a long history of safe use in men and women.
In the original clinical trial by PROTECT investigators, progesterone had consistent and predictable pharmacokinetic properties, did not produce harm, and showed signs of being efficacious for treating acute TBI. In addition, a more recently published human pilot clinical trial by Xiao et al. supports the ProTECT I findings; their study showed a decrease in mortality and an improvement in functional outcome at 6 months with progesterone treatment
In this study, subjects will be enrolled using an Exception from Informed Consent. The justification for this exception is that the preliminary studies indicate that progesterone works best if given as soon as possible after injury and that this drug will only be given to subjects who are unconscious (comatose). If a family member or representative of the patient can provide consent for a potential subject in the first hour of treatment, we will seek that representative's permission.
The possible risks of Progesterone include: blood clots in the legs or lungs that could lead to a heart attack or stroke, raised liver enzymes (a blood test that shows how well the liver is functioning), infection in the lung, blood or tissue around the brain, and other risks not yet known. Potential interactions with other medicines are unlikely, but the study drug will not be given to patients who are allergic to eggs, are pregnant, or who have certain gynecological or breast tumors.
More information is available at the PROTECT III Study website.