Oct. 16, 2006
Progesterone study shows promise for
traumatic brain injury treatment
BY Janet Christenbury
Emory University researchers have found that giving progesterone to trauma victims shortly following brain injury appears to be safe and may reduce the risk of death and the degree of disability. The results of this study—the first clinical trial of its kind—are available in the October issue of Annals of Emergency Medicine. Researchers said the next step will be to confirm their findings in a much larger group of traumatic brain injury (TBI) patients.
“Progesterone treatment for TBI has been extensively studied in laboratory animals for more than 15 years, but this is the world’s first use of progesterone to treat brain injury in humans,” said Arthur Kellermann, Emory professor and chair of the Department of Emergency Medicine and a co-author of the study, which was supported by the National Institute of Neurological Disorders and Stroke.
Approximately 1.5 to 2 million people in the U.S. sustain a TBI each year, leading to 50,000 deaths and 80,000 new cases of long-term disability. It is also a major cause of death and disability among children and military personnel. Despite the enormity of the problem, no new medical therapies have been developed for traumatic brain injuries in more than 30 years.
A three-year pilot study to assess the promise of progesterone for treatment of TBI, called ProTECT (Progesterone for Traumatic brain injury—Experimental Clinical Treatment), enrolled 100 participants. The Phase II study was primarily designed to evaluate whether progesterone can be administered intravenously in a reliable way, and whether the treatment is safe to use in humans with TBI.
In an earlier paper, the researchers reported that progesterone can be reliably given intravenously and achieve predictable levels in the bloodstream. The new paper reports the team’s findings about drug safety and effectiveness.
Enrolled patients had an initial Glasgow Coma Scale score ranging between 4 and 12—an indication of the level of impairment from a TBI—and received either intravenous progesterone or placebo. Thirty days after injury, objective rating scales were used to assess each participant’s neurological function and level of disability.
“We found encouraging evidence that progesterone is safe in the setting of TBI, with no evidence of side effects or serious harmful events,” said David Wright, assistant professor in the Department of Emergency Medicine and lead author of the study. “In addition, we found a 50 percent reduction in the rate of death in the progesterone-treated group. Furthermore, we found a significant improvement in the functional outcome and level of disability among patients who were enrolled with a moderate brain injury.”
The researchers found no significant differences in the rate of adverse events among patients who received progesterone compared to those who received placebo. About 30 percent of patients given placebo died within 30 days of head injury, compared to only 13 percent of those given progesterone. Most patients who died had a severe TBI. Because more severe TBI patients in the progesterone group survived, it is not surprising that they had a higher average level of disability at 30 days than survivors in the placebo group.
One-year outcomes will be reported at a later date.
Donald Stein, Asa G. Candler Professor of Emergency Medicine and neurobiologist at Emory, discovered the neuroprotective properties of progesterone. Progesterone, which exerts protective effects on damaged brain tissue, holds promise as an inexpensive, widely available treatment and has a long track record of safe use in humans to treat other diseases.
The research team is now planning a large, multi-center, Phase III clinical trial designed to test the effectiveness of progesterone in 1,000 patients with TBI, and hopes to secure funding from the National Institutes of Health for this project.