There are currently no approved pharmacologic treatments or strategies for the prevention of post-traumatic stress disorder (PTSD) or other trauma-related sequelae in people who have just been exposed to a traumatic event or life-threatening critical-incident. For the military, it is critical to develop an approach to prevent mental health consequences within hours of exposure to traumatic experiences – during the 'golden hours' – to facilitate resilience in the face of combat exposure. The most ideal intervention would be one that (1) is self-administered and does not require intervention by a physician or psychologist; (2) does not interfere with the recovery process so that it can be safely used in those who would not have developed symptoms; and (3) does not interfere with normal functioning, allowing a return to duty. This application proposes to test a one-time prophylactic treatment for the prevention of symptoms of PTSD and related mental health disturbances and the promotion of resilience: a single dose of hydrocortisone (HCORT), administered within several hours of trauma exposure. HCORT closely resembles the natural cortisol produced in the adrenal glands and released during stress. People at risk for PTSD have demonstrated low cortisol levels before and in the aftermath of trauma. Lower cortisol levels have also been observed in combat Veterans with PTSD. Administering HCORT at the time of trauma would help boost the body's natural stress recovery systems to facilitate resilience. One of the important roles of cortisol is to bring down adrenaline levels and reduce distress and the formation of traumatic memories. HCORT has numerous uses as an anti-inflammatory agent and can be administered safely at the proposed dose without compromising functioning. There are likely to be few, if any, potential contraindications for using HCORT in this manner and in the dose proposed. The use of HCORT to prevent PTSD following traumatic exposure would be akin to using the 'morning after pill' to prevent implantation of a potentially fertilized egg, or administration of a thrombolytic agent to prevent damage resulting from a cerebrovascular event, or a NARCAN rescue kit to prevent respiratory failure following opiate overdose, or an Epi-pen following an allergen. There is now sound pilot data from two prior trials performed by the investigators to warrant enthusiasm for this approach. There is also evidence from animal studies, performed by the investigators, that the treatment administered prophylactically reverses anxiety like behavior and molecular networks in rats exposed to the scent of a predator.
The main aim of the study is to determine whether early intervention with a single dose of HCORT, compared to placebo, administered within several hours following trauma exposure, will reduce the risk of developing PTSD in trauma survivors displaying distress, panic, anxiety or dissociation in the emergency room. Two hundred twenty trauma survivors will be randomized and recruited in two locations: a large urban hospital in New York City, Mount Sinai Hospital, and a large civilian and military hospital in Tel Hashomer, Israel. Trauma survivors will be studied at four time points following treatment, at 2, 6, 12, and 42 weeks post-treatment. It is hypothesized that HCORT treatment will result in an accelerated decline in the presence and severity of mental health symptoms compared to the placebo group. Blood samples will be collected for analysis of potential biomarkers to obtain more information about the mechanisms of action of this intervention. Because we will be performing this research on a mixed group of civilians and military personnel, the information obtained will be relevant to enhancing resilience post-trauma in both military and civilian trauma. If successful, the study will introduce an important, inexpensive, portable, safe and effective tool for combat Veterans to carry with them during a critical incident.
|Effective start/end date||1/01/18 → …|
- Congressionally Directed Medical Research Programs: $5,999,739.00