Atlanta
Researchers to Launch Clinical Trial of Progesterone for Treatment
of Brain Injury
Researchers
from Emory University and Morehouse School of Medicine soon will begin
enrolling patients in the world's first clinical trial of the hormone
progesterone as a treatment for moderate to severe traumatic brain injury,
which annually claims the lives of 50,000 Americans and disables 80,000
more, at an estimated cost of $56 billion. Currently, there is little
that doctors can do for this condition beyond providing supportive care.
The three-year pilot study
is called "ProTECT", which stands for Progesterone for Traumatic brain
injury, Experimental Clinical Treatment. The study has been approved
by the U.S. Food and Drug Administration and is funded by the National
Institutes of Health (NIH). It will be based at Grady Memorial Hospital,
where physicians from Emory will work side-by-side with colleagues from
Morehouse to evaluate a treatment that has proved effective in animal
models but has not yet been tested in humans.
Researchers, led by Emory
University neurobiologist Donald Stein, PhD, have found in a series
of experiments that male and female rats with brain injury develop less
brain swelling and recover more completely when they are treated with
progesterone shortly following injury. The hormone seems to moderate
the inflammation that frequently leads to dangerous brain swelling following
head injury. Progesterone also seems to slow or block a cascade of damaging
chemicals known as free radicals that are unleashed by traumatic injury,
leading to the wholesale death of brain cells. Progesterone occurs naturally
in small amounts in the brains of male and females, both in animals
and in humans.
"Progesterone has been safely
used for decades to treat medical conditions in both women and men,
sometimes for months or even years at a time," said Arthur Kellermann,
MD, MPH, chairman of emergency medicine at Emory and principal investigator
of the new study. "Furthermore, progesterone has been safely given intravenously
to humans at much higher doses than that planned in our study, which
will limit progesterone treatment to only three days."
When corticosteroids, which
were once prescribed to control brain swelling, were found to be ineffective,
emergency physicians and trauma surgeons were left with no effective
therapy for blunt force trauma to the brain. Although barbiturates,
mannitol, and surgery are sometimes used in an attempt to relieve pressure
inside the skull that can occur when a victimÕs brain swells, they are
measures of last resort that may or may not work.
"In contrast to the many
options available to treat other types of injuries," Dr. Kellermann
notes, "brain injury remains the final frontier. We want to take the
crucial next step and determine whether giving progesterone to victims
of moderate to severe traumatic brain injury will save lives and preserve
mental function."
The new study will begin
on May 28th and will enroll up to 100 victims of traumatic brain injury
over the next two years. Four out of five patients (80%) will be administered
progesterone by intravenous infusion for three days. One out of five
patients (20%) will be administered a placebo, consisting of intravenous
fluid without progesterone. Patients will be evaluated for mental functioning
on discharge from the hospital and at one month following injury. Neither
the patients, their families, the doctors or nurses treating them, nor
the study team will know who received progesterone and who did not until
the end of study.
When progesterone is administered
to men, it temporarily suppresses the level of the male hormone testosterone
in the blood. However, when progesterone wears off, testosterone levels
return to normal. Although progesterone may slightly increase the risk
of thromboembolism (blood clots) in the legs or lungs, researchers believe
the risk is minimal compared to the potential benefits for victims of
brain injury.
Most study participants will
be victims of an automobile or motorcycle crash, a fall, or an assault
with a blunt object such as a baseball bat. The study will not enroll
victims of gunshots or other penetrating head wounds.
The study will be open to
all races and both sexes. Pregnant women and individuals suffering from
soybean or egg allergies or cancer of the breast or reproductive organs
will not be eligible. Because the tests used to evaluate recovery have
only been validated among English-speaking patients, enrollment will
be limited to adult English speakers. Since brain-injured patients cannot
think clearly, consent must be granted on their behalf by a family member
or legal representative. To gain entry into the study, patients must
arrive at Grady and a family member must be found to grant consent within
10 hours of injury -- the sooner, the better. If a family member cannot
be located within that time frame, the patient cannot be enrolled in
the study.
Patients will be monitored
closely in the Surgical or Neuro intensive care unit at Grady or in
a new NIH-funded area of Grady called the General Clinical Research
Center. An independent safety committee appointed by the NIH will oversee
the project. This group has the power to end the study early if it is
clear that one treatment group is doing better than the other. If the
results of the pilot phase study are promising, the researchers anticipate
that the study will be extended to additional level I trauma centers
in other US cities in future years.
Rates of traumatic brain
injury are considerably higher in Georgia and in metro Atlanta than
in the country as a whole. In 1999, DeKalb County reported 110 deaths
from traumatic brain injury and Fulton County 193 deaths, ranking them
in the 75th to 90th percentiles nationally among all US counties. In
1999, traumatic brain injury was responsible for 56 deaths at Grady,
out of 429 brain injury patients presenting to the emergency department,
and in 2000, 53 deaths, out of 568 brain injury patients.
"Traumatic brain injury is
one of the most devastating and debilitating injuries anyone can suffer,
and it inflicts its damage disproportionately in metro Atlanta," said
Dr. Kellermann. "We are tremendously excited by the prospect that through
this clinical trial, we may be able to offer hope to those devastated
by brain injury."
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