This study was designed in a parallel fashion with exposure to SSR occurring on one arm without study drug administration (control phase), followed 2 weeks later by exposure to SSR on the contralateral arm with study drug administration (investigative phase) ( Figure 1 b). The MED to experimentally induce sunburn was determined for each participant during the initial screening visit as previously described (). Participants were irradiated with one, two, and three times the MED on the sun-shielded, upper arm using plastic holed templates to ensure that adjacent skin was not exposed. A total of 20 participants completed both phases of the study and were included in the per-protocol analysis.

The Institutional Review Board at University Hospitals Cleveland Medical Center approved this pilot study, which was conducted between March 2013 and February 2015. The study was modeled after a randomized, double-blinded, placebo-controlled trial. The trial is registered with clinicaltrials.gov NCT02920502 ). Twenty-seven healthy adults 18 years and older were screened for eligibility and provided written informed consent ( Figure 1 a). A total of 25 participants were randomized to receive, in a double-blinded fashion, either placebo or a single oral dose of vitamin D(cholecalciferol) at 50,000, 100,000, or 200,000 IU one hour after SSR exposure. UVR was administrated as SSR emitted from a 1,000 W Xenon arc lamp (Newport, Stratford, CT), a full spectrum light source that closely resembles natural sunlight ().

The concentrations of the vitamin Dmetabolites 25(OH)D, 1,25(OH), and 24,25(OH), as well as total serum calcium, were measured from freshly frozen serum obtained during the screening visit, as well as 24 hours, 48 hours, 72 hours, and 1 week after receiving the study drug. Serum levels of 25(OH)D(ng/ml) and 1,25(OH)(pg/ml) were measured by Liaison assay, and serum levels of 24,25(OH)(ng/ml) were measured by liquid chromatography-mass spectrometry (Heartland Assays, Ames, IA). Toxic serum 25(OH)Dlevels were defined as those greater than 150 ng/ml (). Total serum calcium was measured by the University Hospitals Cleveland Medical Center core laboratory (Cleveland, OH), and the normal reference range was considered 8.8–10.7 mg/dl.

Primary outcomes of randomized participants

Primary outcomes included noninvasive measurements of skin erythema and thickness 24 hours, 48 hours, 72 hours, and 1 week after irradiation, as well as tissue expression of TNF-α and iNOS 48 hours after irradiation. Skin erythema (redness) was quantified using a CR300 chromameter (Minolta, Ramsey, NJ). The difference in erythema (Δa∗) between irradiated and nonirradiated skin (a∗ irrad – a∗ nonirrad ) was calculated for each time point after SSR exposure (Δa∗ time ). The difference in Δa∗ time between the investigative and control phases of the study was calculated to determine the effect of the study drug on skin redness after SSR exposure [(Δa∗ time ) invest – (Δa∗ time ) control ].

Skin thickness, an acute measure of edema, was quantified using a Mitutoyo 9 mm dial caliper (Northamptonshire, UK). Thickness measurements were repeated in triplicate and the mean was used for all calculations. The difference in thickness (Δth) between irradiated and nonirradiated skin (th irrad – th nonirrad ) was calculated for each time point after SSR exposure (Δth time ). The difference in Δth time between the investigative and control phases of the study was calculated to determine the effect of the study drug on skin thickness after UVR exposure [(Δth time ) invest – (Δth time ) control ].