Prednisone and other glucocorticoids are considered standard of care for many chronic inflammatory states, and have been approved for some conditions since the 1950s. Prednisone also has a large side effect profile that can limit quality of life, particularly in children. Sleep disturbances are one of the known side effects, as pharmacological doses of prednisone disrupt normal circadian rhythms of endogenous cortisol (the day/night hormone of most organisms).The goal of this Pilot Project it to carry out two specific aims.
The first aim will be to carry out a broad pharmacodynamic biomarker discovery, after a single dose of different doses of prednisone in young adult volunteers (1 mg, 2.5 mg, 10 mg dose groups; 10 subjects/dose), using day -1 time series samples as longitudinal controls. This will initiate defining a systems biology model of the pharmacodynamic effects of prednisone, and will test these at doses lower than have been reported for acute pharmacodynamic biomarkers in the literature (10 mg by Kauh et al. 2012), using a much broader biomarker discovery platform (1,300 proteins tested via SomaScan aptamer platform), and a much denser time series. This will initiate resolving cause/effect aspects of safety that have not been previously attempted via the time series approach. This will also aid in determining the subset of chronic pharmacodynamic safety biomarkers described in U54 RPDP Projects 1 and 2, that are acutely responsive to prednisone (within hours of a single dose).
Aim 2 will query the effect of this single dose of prednisone on sleep patterns, using newly emerging mobile health devices (Microsoft Band). Through previous support of the Clark Charitable Trust Pilot Program, Drs. Hiroki Morizono (CNMC; bioinformatics), Roxanna Bendixen, MD (University of Pittsburgh, Occupational Therapist), and Mr. David Lorenzin (Florence, Italy; app developer) have piloted the Microsoft Band as a clinical outcome device in the community setting, including release of a novel app (CNBandDevice version 1.7.0.0). Here, we will study the sleep patterns of 30 adult volunteers using the Band device for 1 week prior to dosing, the evening of a single prednisone dose, and 1 week after dosing. This will begin to establish baseline data for sleep health of normal volunteers using the Microsoft Band, and determine if a single dose of prednisone induces a dose-response of sleep disturbances. Completion of this Pilot Project will train Dr. Benny Klimek in clinical research (she is currently a basic scientist). While the cost of this pilot cost surpasses the budget permitted in the U54 RPDP pilot, Dr. Benny Klimek received a $70,000 planning grant for this Pilot from the Clark Charitable Trust Pilot Program in 2015, enabling writing of protocols and IRB submissions, and initial training in clinical research. Thus, with the 2 yr pilot funds (@$50,000/yr), completion of this ambitious pilot is feasible.
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