SAN DIEGO—The hormone progesterone is best known for its work in the female reproductive system, where it plays various roles in supporting pregnancy. But starting next month, it will be the focus of a phase III clinical trial for traumatic brain injury (TBI). Researchers hope an infusion of progesterone given within a few hours of a car accident or other trauma will help prevent brain damage, said the trial’s principal investigator, David Wright of Emory University in Atlanta. He described the upcoming trial here today at the annual meeting of the American Association for the Advancement of Science (which publishes ScienceNOW).
The rationale for the trial springs from a chance finding made more than a quarter of century ago. While studying the effects of head injuries in rats, Emory researcher Donald Stein noticed that females had fewer ill effects than did males. Females who were at the progesterone peak of their menstrual cycle did even better. Follow-up studies with other animals also pointed to neuroprotective effects of progesterone, which is present in both the male and the female brain. In recent years, two small clinical trials suggested that progesterone can reduce mortality and disability after TBI in people.
The new trial will provide a sterner test. It aims to enroll 1140 patients at 17 centers across the United States. Each patient will receive an infusion of progesterone starting within 4 hours of his or her injury and lasting 4 days.
Because researchers believe time is of the essence when treating TBI, the U.S. Food and Drug Administration granted a relatively rare “exception to informed consent” for the trial. That means doctors will still be able to administer the hormone even if they are unable to get consent from a patient (who is likely to be unconscious) or an immediate family member within an hour of the patient’s admission to the hospital. In Atlanta, the researchers put up billboards to inform the local community of the trial and established a Web site where people could sign up to be excluded from the trial in the event they suffer a head injury.
Unfortunately, the track record for drug treatments for TBI is not good. Wright estimates that about 50 clinical trials have been conducted to date. All have failed, and at least two were stopped early because they made outcomes even worse. Still, the fact that progesterone seems to act on many different biological pathways may be cause for hope, said Geoffrey Manley, a neurosurgeon at the University of California, San Francisco, one of the centers involved with the new trial. Exactly how the hormone protects the brain is poorly understood, but its effects include suppressing inflammation and preventing injured neurons from self-destructing. “The fact that it’s such a dirty drug may actually be an advantage,” Manley said.