Immune Mechanisms of Vitamin D to Reduce Chronic Pain After Burn

The proportion of patients who are able to follow-up at 6 weeks and complete a questionnaire will be calculated. To meet the primary outcome, follow-up will be >80% at 6 weeks.

Measure the ability of Vitamin D administration to generate sustained increases in whole-blood Vitamin D concentrations (nanograms per deciliter (ng/dl), between baseline and 6 weeks. 25-hydroxyvitamin D concentration will be determined by performing mass spectroscopy on blood spot cards collected at enrollment and at 6 weeks to determine circulating Vitamin D concentration in ng/dl. Mean concentration change from baseline and 6 weeks will be reported for participants in the placebo and intervention group.

To assess safety, adverse events will be tracked through surveys during the 6 weeks after treatment to assess side effects and safety profile of Vitamin D. Adverse Events will be reported using Common Terminology Criteria for Adverse Events (CTCAE). Events will be graded in severity with grade 3 representing severe, grade 4 representing life-threatening, and grade 5 representing death. Relatedness will be categorized as unrelated, unlikely, possible, probable, definite. For this safety measure, we will report the number of grade 3 or higher severity and probable or higher relatedness in the placebo and intervention groups.

Preliminary estimates of efficacy (95% confidence intervals) will be obtained via repeated measures analysis of pain severity over the 1 year following injury using mixed effects models. Pain will be assessed using a 0-10 numeric rating scale with 0 indicating no pain and 10 indicating pain as severe as you can imagine. Higher scores represent worse outcome. These values (collected in identical fashion over 6 months following burn injury) will be entered into a linear mixed model, and overall effect estimates (beta coefficients) among groups will be determined. Unadjusted values will be reported as well as after for adjusting for baseline psychosocial factors (pain catastrophizing, anxiety, depression, stress, perceived social support), sociodemographic factors (age, sex, ethnicity, income, education attainment), and wound healing-related factors. This will be reported over the study period.

Opioid cessation will be defined as the date in which opioids are discontinued for three consecutive days. Median time (days) to opioid cessation will be reported for the treatment and placebo groups.

Use NIH Patient-Reported Outcomes Measurement Information Systems (PROMIS) Neuropathic pain quality to assesses to what degree (from"not at all" to " very much") the respondent's pain shows qualities typical of neuropathic pain in the past 7 days using a 1-5 scale, where 1 indicates "not at all" and 5 indicates "very much." The total scale represented on a scale from 5-25 with 25 representing the highest level of neuropathic pain. This total scale value will be reported for placebo and intervention groups 6 months following treatment.

Use NIH PROMIS Pain interference to determine the extent to which pain interferes with life function. Participants are assessed the degree to which pain interferes with life function across 8 domains. The participants rates interference on a scale of 1 to 5 with 1 representing no interference and 5 representing the maximum interference. The total scale represented on a scale of 8-40 with 40 representing the most interference. Raw scores will be converted to a T score with standard error represented in the derived measure look-up table provided by the NIH PROMIS website. T-scores will be reported for the placebo and intervention groups 6 months following treatment.

Regional Pain Scale (RPS) will be used to assesses pain presence (yes=1, no=0), and severity if present using a 0-10 numeric rating scale. 0-10 scale where 0 indicates no pain and 10 is the worst pain imaginable, for each location of the body (right arm, right, leg, trunk, etc). The mean number of body regions reported as painful (numeric rating scale greater than or equal to 4) will be reported for placebo and intervention groups.

Nociceptive quality of pain will be determined with the NIH PROMIS Nociceptive Pain Quality. Assesses to what degree (from"not at all" to " very much") the respondent's pain shows qualities typical of nociceptive pain in the past 7 days using a 1-5 scale, where 1 indicates "not at all" and 5 indicates "very much." The total scale represented on a scale from 5-25 with 25 representing the highest level of nociceptive pain. Mean total score will be reported for placebo and intervention groups.

Use a custom antibody panel to assess immune cell frequency, and Toll-like receptor 4 (TLR4) activation with phosphorylated NFkB (p-NFkB) as a readout for TLR4 activation). The proportion of immune cells will be determined. Immune cell frequencies multiple parallel mediation model to determine whether immune cells mediate Vitamin D treatment effects. This is an exploratory analysis. Mean proportions of monocytes, cluster of differentiation (CD) 4 T-cells, CD 8 T-cells, neutrophils, mast cells, natural killer-cells will be reported for placebo and intervention groups.