Vitamin D and n-3 Polyunsaturated Fatty Acids (PUFAs) to Prevent Chronic Pain Following Major Thermal Burn Injury

NCT03313076 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 17-1971
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to develop a safe, effective, and readily available treatment that will prevent chronic pain following Major Thermal Burn Injury (MThBI). Burn survivors are prone to develop chronic pain and there is an urgent unmet need for preventative treatments. The preventative treatments proposed for this study, Omega-3 Fatty Acids (O3FA) and Vitamin D have been selected given effectiveness across a range of painful musculoskeletal disorders and their wide availability and low cost. This study is a 2x2 factorial, double-blind, placebo-controlled randomized controlled trial test for the effectiveness of O3FA and Vitamin D to prevent chronic pain development. Burn survivors will be enrolled who have experienced thermal burns that cover less than 30% total body surface area that are severe enough to warrant surgical management, which represents the most common burn injury characteristics. Patients will be enrolled within 72 hours of their burn, and randomized via 1:1:1:1 allocation to receive placebo, O3FA, Vitamin D or both. The investigators will obtain blood samples on enrollment and at 6 weeks to assist in elucidating key mechanisms by which O3FA and Vitamin D reduce chronic pain following MThBI. Chronic pain severity, assessed with a 0-10 numeric rating scale at 6 weeks, 3 months, 6 months and 1 year will be entered into a repeated-measures model. Model estimated contrasts will serve as the primary outcome.

Conditions

Chronic Pain Following Thermal Burn Injury

Keywords

burn injury; thermal burn injury; omega 3 fatty acids; vitamin D; fish oil; chronic pain; chronic pain due to trauma

Outcome Measures

Primary Outcomes (3)

• Qualitative Review of Treatment-Related Adverse Events

  A primary objective of this pilot study is to ensure safety of both treatments as well as combined. A qualitative review of treatment-related adverse events will be performed and a determination about the degree of relatedness of each adverse event with the intervention using CTCAE criteria will be made as CTCAE criteria assesses relatedness to therapy. Investigator reviewing the details of each adverse event rated the likelihood of relatedness to the study drug on a scale: (unrelated, unlikely, possible, probably, definitely).

  6 weeks following burn injury

• Percent of Participants Who Are Compliant With Follow-up (Feasibility)

  The primary objective of this pilot study is to ensure that the investigators are able to make follow-up assessments on a majority of participants. The percent of participants who are compliant with follow-up will be determined 6 weeks following major thermal burn injury. Feasibility is defined as \>80% of enrolled participants at 6 weeks following Major Thermal Burn Injury (MThBI).

  6 weeks following burn injury

• By Group Efficacy Estimates Over Year Following Thermal Burn Injury

  Estimates of efficacy 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. Final model was a piece-wise linear mixed model, with a cut-point at 6 weeks. Mixed models were adjusted for age, sex, race, initial pain severity. Every 1 unit change in beta coefficient represents a 1 unit change in pain severity on the 0-10 numeric rating scale.

  Over 1 year following MThBI

Secondary Outcomes (4)

• Sex Differences in Treatment Response Based on Pain Scores

  6 weeks following burn injury

• General Mental Health as Measured by the Short Form (SF)-12 General Mental Health Component Scores

  6 weeks following burn injury

• General Physical Health by Treatment Group Measured by the SF-12 General Physical Health Component Scores

  6 weeks following burn injury

• Pain Interference by Treatment Group Measured by the Brief Pain Inventory

  6 weeks following burn injury

Study Arms (4)

n-3 PUFA (O3FA) + Vitamin D3

EXPERIMENTAL

4g fish oil in 4 softgels (n-3 PUFA/O3FA) + 2000 IU Vitamin D3 in 1 capsule

Drug: Omega-3 fatty acids (fish oil); Drug: Vitamin D3 (cholecalciferol)

n-3 PUFA (O3FA) Placebo + Vitamin D3

EXPERIMENTAL

4g of corn/soy oil blend in 4 softgels + 2000 IU Vitamin D3 in 1 capsule

Drug: Vitamin D3 (cholecalciferol); Drug: Omega-3 fatty acid placebo

n-3 PUFAs (O3FA) + Vitamin D3 Placebo

EXPERIMENTAL

4g fish oil in 4 softgels (n-3 PUFA/O3FA) + Vitamin D3 matching Placebo, an inert white powder placebo in 1 capsule

Drug: Omega-3 fatty acids (fish oil); Drug: Vitamin D3 (cholecalciferol) placebo

n-3 PUFA (O3FA) Placebo + Vitamin D3 Placebo

PLACEBO COMPARATOR

4g n-3 PUFA/O3FA Matching Placebo, a corn/soy oil blend in 4 softgels + inert white powder Vitamin D3 matching placebo in 1 capsule

Drug: Vitamin D3 (cholecalciferol) placebo; Drug: Omega-3 fatty acid placebo

Interventions

Omega-3 fatty acids (fish oil) DRUG

4 capsules comprising approximately 2 grams of Eicosapentaenoic acid/Docosahexaenoic acid (EPA/DHA) in a 3:2 ratio (this will require a total dose of 4 grams of fish oil). This will be administered daily, by mouth for 6 weeks

Also known as: Fish oil, n-3 fatty acids

n-3 PUFA (O3FA) + Vitamin D3; n-3 PUFAs (O3FA) + Vitamin D3 Placebo

Vitamin D3 (cholecalciferol) DRUG

1 capsule containing 2000 IU of Vitamin D3. This will be administered daily, by mouth for 6 weeks following enrollment.

Also known as: Cholecalciferol, Vitamin D3

n-3 PUFA (O3FA) + Vitamin D3; n-3 PUFA (O3FA) Placebo + Vitamin D3

Vitamin D3 (cholecalciferol) placebo DRUG

1 capsule containing inert substance. This will be administered daily, by mouth for 6 weeks following enrollment.

Also known as: Placebo, inert white powder, Vitamin D3 Matching Placebo

n-3 PUFA (O3FA) Placebo + Vitamin D3 Placebo; n-3 PUFAs (O3FA) + Vitamin D3 Placebo

Omega-3 fatty acid placebo DRUG

4g of corn/soy oil blend in 4 softgels. This will be administered daily, by mouth for 6 weeks following enrollment.

Also known as: Placebo, corn/soy oil soft gels, PUFA Matching Placebo

n-3 PUFA (O3FA) Placebo + Vitamin D3; n-3 PUFA (O3FA) Placebo + Vitamin D3 Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years and ≤ 65 years of age
• Admitted to burn center within 72 hours of thermal burn injury
• Estimated Total Body Surface area (TBSA) ≤ 30%
• Surgical team has plans for surgical management of the burn wound (e.g. xenograft and/or autograft).
• Patients experience a thermal burn injury, not an electrical or chemical burn.
• Has a telephone to receive follow-up calls.
• Able to speak and read English
• Resides within 150 miles of study site
• Alert and oriented
• Willing to take study medication for 6 weeks following enrollment
• Subjects are capable of giving informed consent.
• Predicted probability of chronic pain ≥ 0.3 when demographic parameters are entered into a logistic regression model developed from a previous cohort. (Initial pain score entered into this model will be based on the highest pain severity over the initial 24 hours of hospital admission).
• European American or African American

You may not qualify if:

• Unwilling to take study drug
• Allergy to fish oil or corn/soybean oil.
• Patient taking clopidogrel (Plavix)
• Patient taking warfarin or dabigatran.
• Substantial comorbid injury (e.g. long bone fracture)
• Pregnancy/Breastfeeding
• Prisoner status
• Chronic daily opioid use prior to burn (\>20 mg oral daily morphine equivalents).
• Active psychosis, suicidal ideation, or homicidal ideation
• Requires an escharotomy or fasciotomy for the treatment of burn injury.
• Has a disorder of pain processing or diminished capacity to perceive pain (congenital insensitivity to pain)
• Known Child-Pugh liver disease severity classification B or C.
• Known chronic kidney disease stage 4 or higher (GFR≤29).
• Known Hemophilia A/B
• Known bleeding dyscrasia

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

University Of North Carolina

Chapel Hill, North Carolina, 27517, United States

Location

MeSH Terms

Conditions

Burns; Chronic Pain

Interventions

Fatty Acids, Omega-3; Fish Oils; Cholecalciferol

Condition Hierarchy (Ancestors)

Wounds and Injuries; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Oils; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids

Limitations and Caveats

Early termination because of pandemic delays

Results Point of Contact

• Title: Matt Mauck, MD, PhD
• Organization: University of North Carolina at Chapel Hill

matt_mauck@med.unc.edu

919-966-5136

Study Officials

• Matthew C Mauck, MD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2x2 Factorial design

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: October 18, 2017
• Study Start: July 19, 2018
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: March 17, 2025
• Results First Posted: July 26, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: 12-36 months following publication
• Access Criteria: Deidentified individual data that supports the results will be shared 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 UNC independently.

Locations

US (1)