Vitamin D and n-3 Polyunsaturated Fatty Acids (PUFAs) to Prevent Chronic Pain Following Major Thermal Burn Injury
Condition: Chronic Pain Following Thermal Burn Injury
MeSH terms: Chronic Pain; Wounds and Injuries; Burns
Intervention: Omega-3 fatty acids (fish oil); Vitamin D3 (cholecalciferol); Vitamin D3 (cholecalciferol) placebo; Omega-3 fatty acid placebo
Intervention description: 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; 1 capsule containing 2000 IU of Vitamin D3. This will be administered daily, by mouth for 6 weeks following enrollment.; 1 capsule containing inert substance. This will be administered daily, by mouth for 6 weeks following enrollment.; 4g of corn/soy oil blend in 4 softgels. This will be administered daily, by mouth for 6 weeks following enrollment.
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: 2x2 Factorial design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double-blind
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: burn injury; thermal burn injury; omega 3 fatty acids; vitamin D; fish oil; chronic pain; chronic pain due to trauma

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.
    

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

          -  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

        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.

          -  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

          -  History of an inability to tolerate fish oil or corn/soybean oil.

          -  Severe gastroesophageal reflux disease

          -  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

          -  Hypercalcemia (if not already completed, this will be assessed by clinical labs with
             albumin correction prior to enrollment).

          -  Hypervitaminosis

          -  Sarcoidosis

          -  Hyperphosphatemia

          -  Arteriosclerosis

          -  Active myocardial ischemia

          -  Frequent antacid use (calcium carbonate, cimetidine)

          -  Cholestyramine or Colestipol use

          -  Taking Vitamin D supplements in excess of 800 IU daily.

          -  Taking >1g of fish oil per day.