Pilot, Double-blind, Randomized Controlled, Multi-center Study of the Effects of Fish Oil and Vitamin D in the Prevention of Chronic Pain Following Major Thermal Burn Injury
Overview
- Phase
- Phase 2
- Intervention
- Omega-3 fatty acids (fish oil)
- Conditions
- Chronic Pain Following Thermal Burn Injury
- Sponsor
- University of North Carolina, Chapel Hill
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- By Group Efficacy Estimates Over Year Following Thermal Burn Injury
- Status
- Terminated
- Last Updated
- last year
Overview
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.
Detailed Description
Patients will be screened daily. Patients who meet eligibility criteria will be approached for participation. Patients interested in participating will proceed through informed consent. Once informed consent is obtained, an initial questionnaire will be administered, a blood draw will be performed to assess for baseline Vitamin D/O3FA concentration and immune profile. Then patients will be randomized into one of 4 treatment arms in 1:1:1:1 allocation. Patients will receive study drug for 6 weeks following burn injury. Adverse event monitoring will occur daily while inpatient and weekly once discharged from the hospital through 6 weeks. Patient compliance with the study drug will be assessed via patient-reported reported missing doses, pill counts at the end of the study, and a 6-week blood draw in which Vitamin D/O3FA levels and immune profile will be assessed. Patient-reported outcomes will be collected via follow-up survey at 6 weeks, 3 months, 6 months, and 1 year following burn injury.s, and 1 year following burn injury.
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥ 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
Exclusion Criteria
- •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.
Arms & Interventions
n-3 PUFA (O3FA) + Vitamin D3
4g fish oil in 4 softgels (n-3 PUFA/O3FA) + 2000 IU Vitamin D3 in 1 capsule
Intervention: Omega-3 fatty acids (fish oil)
n-3 PUFA (O3FA) + Vitamin D3
4g fish oil in 4 softgels (n-3 PUFA/O3FA) + 2000 IU Vitamin D3 in 1 capsule
Intervention: Vitamin D3 (cholecalciferol)
n-3 PUFA (O3FA) Placebo + Vitamin D3
4g of corn/soy oil blend in 4 softgels + 2000 IU Vitamin D3 in 1 capsule
Intervention: Vitamin D3 (cholecalciferol)
n-3 PUFA (O3FA) Placebo + Vitamin D3
4g of corn/soy oil blend in 4 softgels + 2000 IU Vitamin D3 in 1 capsule
Intervention: Omega-3 fatty acid placebo
n-3 PUFAs (O3FA) + Vitamin D3 Placebo
4g fish oil in 4 softgels (n-3 PUFA/O3FA) + Vitamin D3 matching Placebo, an inert white powder placebo in 1 capsule
Intervention: Omega-3 fatty acids (fish oil)
n-3 PUFAs (O3FA) + Vitamin D3 Placebo
4g fish oil in 4 softgels (n-3 PUFA/O3FA) + Vitamin D3 matching Placebo, an inert white powder placebo in 1 capsule
Intervention: Vitamin D3 (cholecalciferol) placebo
n-3 PUFA (O3FA) Placebo + Vitamin D3 Placebo
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
Intervention: Vitamin D3 (cholecalciferol) placebo
n-3 PUFA (O3FA) Placebo + Vitamin D3 Placebo
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
Intervention: Omega-3 fatty acid placebo
Outcomes
Primary Outcomes
By Group Efficacy Estimates Over Year Following Thermal Burn Injury
Time Frame: Over 1 year following MThBI
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.
Percent of Participants Who Are Compliant With Follow-up (Feasibility)
Time Frame: 6 weeks following burn injury
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).
Qualitative Review of Treatment-Related Adverse Events
Time Frame: 6 weeks following burn injury
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).
Secondary Outcomes
- Pain Interference by Treatment Group Measured by the Brief Pain Inventory(6 weeks following burn injury)
- 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)