Santa Clara Valley Medical begins study on traumatic brain injuries

Starting this month, someone rushed to Santa Clara Valley Medical Center with a traumatic brain injury may get a shot of a sex hormone.
The hospital is joining Stanford, San Francisco General and about a dozen hospitals across the country to test if progesterone, a hormone pregnant women produce in abundance, can stop the brain from wreaking self-destruction after an accident.

Neuroscientists say the trial is the most promising in decades to find a drug that can treat traumatic brain injury, or TBI, which afflicts 1 million to 2 million Americans each year. Researchers say the illness has been chronically underfunded and understudied, but is now stepping into the limelight as the signature illness of the wars in Iraq and Afghanistan.

Currently, no drug exists to stop the brain from swelling a few hours after a blow to the head, commonly from a car crash, an accidental fall, or in Iraq, a blast from an improvised explosive. Swelling causes bystanding brain cells to die and under extreme pressure, the brain can leak out of the base of the skull, killing the patient. Progesterone may halt the brain from bulging and protect brain cells around the injury.

Few drugs have shown promise to treat TBI. For the past three decades, "all of the clinical trials have failed," said Geoffrey Manley, chief of neurosurgery at San Francisco General Hospital. Two studies were halted when the drugs made patients worse. But in a 100-person trial at an Atlanta hospital between 2001 and 2005, TBI patients given progesterone were more than twice as likely to survive than those given a placebo. Patients with a moderate brain injury were more likely to recover if given progesterone. And progesterone, which occurs naturally in both men and women and is packaged in birth-control pills, has well-understood and limited side effects.

In the next five years, 1,140 patients will be enrolled in the study.

The progesterone must be administered within four hours, about the time it takes a blow to the head to begin perverting the brain's chemistry. Since brain injured patients are likely unconscious when rushed to the hospital and can't give consent, the study has an FDA exception to enroll a patient if a medical proxy can't be found.

The war in Iraq has done more than anything else to elevate traumatic brain injuries to the public consciousness, according to neurosurgeon Dr. Roland Torres at Santa Clara Valley Medical, who oversees about a thousand TBI cases each year. "All of a sudden, there was an incredible amount of money to do studies on brain injury," Torres said. Nearly US$400 million in research grants for TBI were awarded by the Department of Defense, Veteran's Affairs, and Health and Human Services between 2003 and 2008, which doctors say is a dramatic increase from the 1990's. "It was sort of a blessing in disguise," Torres says.

If this trial shows progesterone is effective in treating TBI, soldiers will add injectable progesterone to their medical kits, and paramedics could give it at the site of a car wreck.

Torres believes one reason TBI has been underfunded is that nurses and doctors often see brain injured patients go in wheelchairs to nursing homes, but rarely get to see the patients who recover and return to school or work.