Progesterone is one of the most exciting things we have coming out,” said Lori Shutter, director of neurocritical care at the University of Cincinnati Hospital, one of the 17 study sites. “You can’t undo the initial injury, but you hope to reduce the secondary injury, and progesterone may have a role in reducing the inflammatory process.”
Wall Street Journal
JUNE 23, 2009
Brain-Trauma Study Set
By THOMAS M. BURTON
Several potential treatments for brain injury and stroke have failed in recent clinical studies, but one improbable therapy — the hormone progesterone — continues to show promise in warding off brain damage from head trauma and stroke.
In the latest development, the National Institutes of Health are expected Tuesday to begin funding a study evaluating the hormone in more than 1,100 emergency patients with moderate to severe head trauma.
This study will get under way at 17 hospitals in 15 states around the U.S. and is expected to last up to five years at a projected cost of up to $28 million. It will be the pivotal study of whether the naturally occurring hormone progesterone, injected into patients within hours of severe accidents, can lower deaths and reduce paralysis and cognitive damage. It will be the definitive test of earlier animal research conducted over a quarter century by Emory University brain researcher Donald G.Stein, the subject of a page-one Wall Street Journal article two years ago.
“The extensive laboratory science and preliminary clinical research is highly promising, but not definitive,” said David Wright, the Emory emergency-medicine doctor who will be principal investigator of the research. “This study is the ultimate test.”
In recent years, various potential neurological treatments for stroke and brain injury have failed, such as the use in ambulances of high-concentration saline to relieve cranial pressure in brain-injury patients, and cooling procedures, or hypothermia, in pediatric brain-injury patients. These are only some of the latest disappointments in finding potential “neuro-protective” agents.
As a result, the idea that progesterone might be beneficial is greeted with both skepticism and considerable hope.
“Progesterone is one of the most exciting things we have coming out,” said Lori Shutter, director of neurocritical care at the University of Cincinnati Hospital, one of the 17 study sites. “You can’t undo the initial injury, but you hope to reduce the secondary injury, and progesterone may have a role in reducing the inflammatory process.”
In the past few years, Dr. Stein’s lab at Emory has focused on using progesterone in treating clot-caused strokes, the most common form of stroke and one that is estimated to afflict more than 80% of the 700,000 U.S. stroke patients annually. In laboratory rats, progesterone, derived from yams but also present as a human hormone, has shown success in Dr. Stein’s lab in reducing the size of the brain tissue that is destroyed after a stroke.
“You can give progesterone up to six hours after the stroke and still get significant benefits,” said Dr. Stein. This is animal research, but it is consistent with his lab’s findings over decades. The six-hour window could prove especially important in stroke, since the main treatment now for the condition, a drug called tPA, has so far been definitively shown to be effective for only a three-hour window after a stroke.
Progesterone is often thought of as a sex hormone, since it occurs in female mammals at higher rates than in males, especially during pregnancy and menstruation. The notion that it could be helpful against brain injury arose as an accidental finding. Dr. Stein and his colleagues noticed that when lab animals’ brains were injured artificially, many female rats totally avoided cognitive loss even though males lost brain function.
Most recently, his research has involved duplicating the effect of a clot in a rat’s brain and finding that “we got substantial neuroprotection,” said Dr. Stein. The protective effect has helped in animals’ motor performance, grip strength and cognitive ability — all capacities that are damaged in both stroke and brain injury.
Dr. Stein’s lab recently won a grant from the Centers for Disease Control and Prevention to study, in lab animals, the use of progesterone for pediatric brain injuries. He also is in initial stages of working with the U.S. military to evaluate the hormone in battlefield wounds.
In the upcoming brain-trauma trial, patients will be randomly assigned to receive progesterone plus standard therapy to stabilize head injuries, or will be part of a control group receiving standard therapy alone. One potentially controversial aspect of the study is that it will be given to patients without consent, largely because time is of the essence and patients’ families often can’t be located for hours. No patient will have any standard treatment withheld, however.
Printed in The Wall Street Journal, page D3