Progesterone was observed to improve treatment and recovery in women after traumatic brain injury (TBI), prompting interest in clinical trials to see how the hormone would fare. Unfortunately, a study has shown that the hormone was no more effective than placebo in treating TBI.
Published in the New England Journal of Medicine, the study was called ProTECT III. It was originally planned that 1,140 TBI patients would be included but the number was cut to 882 after it was determined that additional enrollment would not be beneficial anyway. From July 2009 to November 2013, favorable and survival outcomes (as measured by improvements in Glasgow Coma Scores) were assessed in patients across 49 trauma centers in the United States and results showed that there was not a significant difference between the scores of the progesterone-treated group and the placebo group.
In those who were given the hormone, favorable outcomes were present in 51 percent of the progesterone-treated group while those given placebos registered 56 percent. In terms of mortality rates after six months, the progesterone-treated group logged 18.8 percent while the placebo group got 15.7 percent.
According to David Wright, M.D., emergency medicine research vice chair and associate professor at Emory University and lead investigator for the study, results were plainly disappointing. Preclinical data on progesterone's neuroprotective effects were compelling but unfortunately did not translate to the clinical trial with TBI patients.
Progesterone is a naturally occurring hormone in both men and women, a steroid produced to support reproductive functions and brain development. It was administered by infusion through a four-day period and was generally tolerated well, with similar adverse effects in both groups. Phlebitis, a vein inflammation, however, was more prevalent in the progesterone-treated group.
"The trial results were not what we had hoped. Scientists must now redouble their efforts to develop treatments that protect the brain and enhance its natural recovery mechanisms," said Walter Koroshetz, M.D., National Institute of Neurological Disorders and Stroke acting director.
He added that animal studies must be aggressively pursued to establish desired effects in people before late-stage trials are started as this will clue researchers in on the right amount and duration for a dose.
Supported by the National Institute of Neurological Disorders and Stroke, the study was organized as part of the Neurological Emergencies Treatment Trials network. Researchers from the University of Michigan provided coordination and oversight while the Medical University of South Carolina took care of data analysis. Emory neurology professor Michael Frankel, M.D. also pitched in as principal investigator on-site at the Grady Memorial Hospital.