PROJECT SUMMARY/ABSTRACT
Post traumatic stress disorder (PTSD) is linked to accelerated aging and is associated with increased risk of
early-onset cardiovascular disease (CVD) in both men and women. PTSD is associated with premature
vascular aging (i.e., large elastic arterial stiffening and vascular endothelial dysfunction) and autonomic
dysfunction (e.g., reduced cardiovagal baroreflex sensitivity [cBRS] and heart rate variability [HRV]), key
antecedents in the development of CVD. Sleep is important for cardiovascular health via cellular and tissue
repair, free radical detoxification and reducing oxidative stress and inflammation. Nightmares, a central feature
of PTSD, are a debilitating condition that can lead to sleep deprivation or insomnia, daytime sleepiness and
other sequala, that ultimately causes clinically significant distress and impairment in social, occupational and
cardiovascular function. As such, therapeutic strategies and interventions that address nightmare-associated
sleep disturbances in individuals with PTSD is clinically important for improving sleep quality, cardiovascular
health and risk for future age-associated CVD. NightWare™ digital therapeutic system is a novel smart watch
application that was recently granted Breakthrough Device designation by the FDA for the treatment of
nightmares in adults with PTSD. It uses machine learning to detect, track and arouse an individual out of a
nightmare by sending vibrotactile feedback to a smart watch, and arousing the individual out of the nightmare
without awakening and disrupting sleep. In the present R21 we are proposing a randomized, double-blind,
placebo (i.e., sham intervention) controlled parallel pilot study that will provide the first clinical evidence for the
efficacy of the NightWare digital therapeutic system to improve cardiovascular health outcomes in adults with
nightmares associated with PTSD. An additional goal of this R21 will be to obtain exploratory mechanistic
insight by which NightWare improves cardiovascular function, specifically, related to sleep quality, nitric oxide
bioavailability, free radical production, oxidative stress and inflammation. We hypothesize that 6 weeks of the
NightWare intervention will improve outcomes of vascular aging (e.g., large elastic arterial stiffening, vascular
endothelial dysfunction) and autonomic function (cBRS, HRV) in adults with PTSD-related nightmares. The
results from this pilot investigation will provide the basis for a larger randomized clinical trial that would be
conducted to establish the efficacy of NightWare as a safe and effective therapeutic strategy for treating
nightmares, promoting healthy vascular aging, autonomic function and reducing the risk for CVD later in life in
adults with nightmares associated with PTSD.