Could Taking a Drug Within a Few Hours of a Trauma Help Avert Post Traumatic Stress Disorder?
Mount Sinai Receives $6 Million Award from United States Department of Defense to Study Oral Hydrocortisone for PTSD Prevention
Researchers at the Icahn School of Medicine at Mount Sinai have been awarded nearly $6 million through a U.S. Army Medical Research grant to test whether a one-time dose of a drug—oral hydrocortisone (HCORT)—can prevent post-traumatic stress disorder (PTSD) and related mental health disturbances in both civilians and military personnel.
Oral hydrocortisone is a synthetic glucocorticoid similar to the body’s own cortisol and has numerous clinical uses as an anti-inflammatory agent. In response to acute stress, ample cortisol levels are critical to activating, and then containing, body systems that are mobilized as part of the fight-or-flight response. Previous studies have shown that people with lower cortisol levels at the time of trauma exposure are at elevated risk for PTSD.
This study, titled “PTSD Prevention Using Oral Hyrdocortisone in the Immediate Aftermath of Trauma,” is based on the hypothesis that a single administration of HCORT within six hours after trauma will facilitate cortisol-induced suppression of adrenaline that might otherwise lead to the “over-consolidation” of traumatic memories implicated in PTSD, therefore leading to quicker and greater recovery.
“Our team has already conducted two trials that provided sound pilot data to support this hypothesis,” says Rachel Yehuda, PhD, Professor of Psychiatry, and Neuroscience, at the Icahn School of Medicine at Mount Sinai, a recognized scientific expert on resilience and Principal Investigator of the study. “If successful, this work could lead to an easily administered, inexpensive, and portable intervention that doesn’t require evaluation of risk or vulnerability prior to or after trauma exposure. This resilience-enhancing intervention would be safe for both men and women, and could be administered to people who would not otherwise develop PTSD without harm or consequence.”
Specifically, this will be a two-site, double-blind, randomized, placebo-controlled trial conducted on 220 recently traumatized patients presenting to the emergency departments of two large hospitals: The Mount Sinai Hospital in New York City, which serves a diverse population of civilians, and Chaim Sheba Medical Center in Israel, which serves both civilians and military personnel.
Study participants will receive a single oral dose of HCORT or placebo within six hours following their trauma and will be subsequently assessed at 2, 6, 12, and 42 weeks. After ingestion of the HCORT or placebo, blood will be drawn for baseline biological assessment. Symptoms will be assessed and blood and salivary cortisol samples will be obtained at each subsequent visit. The collection of biological samples at each time point will allow verification of mechanism of action of the HCORT intervention. Biological assessments include plasma cortisol and adrenocorticotrophin hormone, whole blood NR3C1 and FKBP5 gene methylation and expression, salivary circadian rhythm of cortisol, plasma neuropeptide Y, cytokines and immune markers, and sympathetic nervous system activity.
The particular aims of the study are (1) to determine whether early intervention with a single dose of HCORT will reduce the risk of PTSD in trauma survivors displaying distress in the emergency department, (2) to evaluate whether HCORT alters the trajectory of a range of mental health symptoms including anxiety, depression, dissociation, and disrupted sleep, (3) to determine whether acute hormonal and related molecular responses to trauma predict the development of PTSD (in the placebo condition) or its prevention by HCORT, and (4) to assess biological measures over time in those receiving HCORT versus placebo to establish whether biological changes associated with resilience have occurred.
“The military has a critical need for a highly portable, easily administered intervention that can attenuate acute symptoms and prevent longer-term mental health consequences following critical incidents,” says Dr. Yehuda. “But if the study shows that rapid HCORT administration helps prevent PTSD, the intervention will dramatically improve patient care for military personnel and civilians by mitigating the impact of trauma.”
This grant supports an international, collaborative study between the Icahn School of Medicine at Mount Sinai and Chaim Sheba Medical School in Israel. These two academic research institutions have collaborated on previous related studies.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.