Immune Mechanisms of Vitamin D to Reduce Chronic Pain After Burn

Immune Mechanisms of Vitamin D in a Randomized Controlled Trial to Reduce Chronic Pain After Burn

The goal of this pilot clinical trial is to learn whether vitamin D is able to prevent chronic pain following burn injury and to determine what biological mechanisms are engaged by Vitamin D following burn injury. The main question[s] it aims to answer are:

• Is the clinical trial protocol feasible?
• Is Vitamin D administration following burn injury safe?
• How does vitamin D cause changes in the immune system in the aftermath of burn injury?

Following informed consent, participants will be asked to:

• Take 6 capsules by mouth one time following burn injury (Vitamin D or Placebo)
• Provide a blood sample at baseline and 6 weeks following injury
• Fill out surveys daily while in the hospital, weekly through 6 weeks, and at 3 months and 6 months.

Researchers will compare Vitamin D and placebo groups to see if there are differences in adverse effects (side effects), chronic pain, and profiles of immune cells from collected blood samples.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Burn Injury
• Intervention / Treatment: Drug: Ergocalciferol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• ≥ 18 years and ≤ 70 years of age
• MThBI severe enough to warrant admission to Burn Surgery Service (NOTE: surgery may or may not be indicated)
• Admission and subsequent enrollment occurs within 1 week of MThBI
• Patients experience a thermal burn injury, not an electrical or chemical burn.
• Has a smartphone with continuous service >1 year
• Alert and oriented
• Willing to take study medication (6 capsules of Vitamin D or placebo)
• Point of care Vitamin D level <100 ng/mL
• Able to speak and read English
• Burn survivors with acute pain severity ≥ 7/10 on the Numeric Rating Scale (initial pain severity reported by patient on screening)
• Total Body surface area burned <30%

Exclusion Criteria

• Substantial comorbid injury (e.g. long bone fracture)
• Pregnancy/Breastfeeding
• Prisoner status
• Active psychosis, suicidal ideation, or homicidal ideation
• Requires an emergency/bedside escharotomy or fasciotomy for the treatment of burn injury.
• Known Child-Pugh liver disease severity classification B or C.
• Known chronic kidney disease stage 4 or higher (GFR≤29).
• No other history or condition that would, in the investigator's judgment, indicate that the patient would very likely be non-compliant with the study or unsuitable for the study (e.g. might interfere with the study, confound interpretation, or endanger patient).
• Intubated and sedated at time of enrollment.
• Hypersensitivity to Vitamin D3, ergocalciferol, calcitriol, alfacalcidol, calcipotriol
• Known hypercalcemia (based on routine admission laboratory assessment).
• Sarcoidosis
• Hyperphosphatemia (based on routine admission laboratory assessment)
• Taking Vitamin D supplements in excess of 800 IU daily.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D2 (Ergocalciferol); One time, oral dose of Vitamin D2 administered via 6 50,000 IU Ergocalciferol capsules. Capsules will be encapsulated and masked to be indistinguishable from placebo.	Drug: Ergocalciferol; One-time, oral dose of 300,000 IU of Ergocalciferol administered via 6 capsules.; Other Names: Vitamin D2, Calciferol, Drisdol
Placebo Comparator: Placebo; One time, oral dose of 6 placebo capsules filled with inert powder and encapsulated and masked to be indistinguishable from active comparator.	Drug: Placebo; One-time, oral dose of 6 inert capsules matched to the active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Follow-up rate 6 weeks following burn injury	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.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
25-hydroxyvitamin D concentration 6 weeks after Vitamin D2 treatment	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.	Baseline, 6 weeks
Safety of Vitamin D2 administration in aftermath of burn injury	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.	6 weeks
Opioid cessation	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.	6 months
Neuropathic pain quality	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.	6 months
Pain Interference	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.	6 months
Widespread pain severity	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.	6 months
Nociceptive quality	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.	6 months
By Group Efficacy Estimates Over Year Following Thermal Burn Injury	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.	Baseline, 1 week, 2 week, 3 week, 4 week, 5 week, and 6 weeks, 3 months, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory immune cells populations assessed with mass cytometry	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.	6 weeks

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Matthew Mauck, MD, PhD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Actual): January 16, 2026
• Study Completion (Actual): January 16, 2026

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 8, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Wounds and Injuries; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Pain; Burns; Lipids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Ergocalciferols; Cholecalciferol
• Other Study ID Numbers: 22-1310; K23AT011389-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared on request provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with the University of North Carolina (UNC).
• IPD Sharing Time Frame: starting 12 and continuing for 36 months after publication
• IPD Sharing Access Criteria: Approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No