search
Back to results

Immune Mechanisms of Vitamin D to Reduce Chronic Pain After Burn

Primary Purpose

Burn Injury, Chronic Pain

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ergocalciferol
Placebo
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Burn Injury

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria ≥ 18 years and ≤ 70 years of age Admitted to burn center Surgical team has plans for surgical management of the burn wound (e.g. xenograft and/or autograft, NOTE: in some burn patients the plan will change, but if there is documentation in the note or in communication with the surgical team there are plans for surgical management then the patient will be eligible) 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 the 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.

Sites / Locations

  • University Of North CarolinaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Vitamin D2 (Ergocalciferol)

Placebo

Arm Description

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.

One time, oral dose of 6 placebo capsules filled with inert powder and encapsulated and masked to be indistinguishable from active comparator.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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 1 year 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
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.
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.
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.
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.
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.

Full Information

First Posted
November 1, 2022
Last Updated
October 18, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Center for Complementary and Integrative Health (NCCIH)
search

1. Study Identification

Unique Protocol Identification Number
NCT05619289
Brief Title
Immune Mechanisms of Vitamin D to Reduce Chronic Pain After Burn
Official Title
Immune Mechanisms of Vitamin D in a Randomized Controlled Trial to Reduce Chronic Pain After Burn
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 12, 2023 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Center for Complementary and Integrative Health (NCCIH)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Burn Injury, Chronic Pain

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Vitamin D2 (Ergocalciferol)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One time, oral dose of 6 placebo capsules filled with inert powder and encapsulated and masked to be indistinguishable from active comparator.
Intervention Type
Drug
Intervention Name(s)
Ergocalciferol
Other Intervention Name(s)
Vitamin D2, Calciferol, Drisdol
Intervention Description
One-time, oral dose of 300,000 IU of Ergocalciferol administered via 6 capsules.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One-time, oral dose of 6 inert capsules matched to the active comparator
Primary Outcome Measure Information:
Title
Follow-up rate 6 weeks following burn injury
Description
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.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
25-hydroxyvitamin D concentration 6 weeks after Vitamin D2 treatment
Description
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.
Time Frame
Baseline, 6 weeks
Title
Safety of Vitamin D2 administration in aftermath of burn injury
Description
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.
Time Frame
6 weeks
Title
By Group Efficacy Estimates Over Year Following Thermal Burn Injury
Description
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 1 year 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.
Time Frame
Baseline, 1 week, 2 week, 3 week, 4 week, 5 week, and 6 weeks, 3 months, 6 months
Title
Opioid cessation
Description
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.
Time Frame
6 months
Title
Neuropathic pain quality
Description
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.
Time Frame
6 months
Title
Pain Interference
Description
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.
Time Frame
6 months
Title
Widespread pain severity
Description
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.
Time Frame
6 months
Title
Nociceptive quality
Description
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.
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Inflammatory immune cells populations assessed with mass cytometry
Description
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.
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria ≥ 18 years and ≤ 70 years of age Admitted to burn center Surgical team has plans for surgical management of the burn wound (e.g. xenograft and/or autograft, NOTE: in some burn patients the plan will change, but if there is documentation in the note or in communication with the surgical team there are plans for surgical management then the patient will be eligible) 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 the 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Matthew Mauck
Phone
919-966-5136
Email
matt_mauck@med.unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Mauck, MD, PhD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27517
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew C Mauck, MD PhD
Phone
919-966-5136
Email
matt_mauck@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Matthew C Mauck, MD PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

Immune Mechanisms of Vitamin D to Reduce Chronic Pain After Burn

We'll reach out to this number within 24 hrs