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

NCT ID: NCT03313076

Last Updated: 2025-03-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-19
• Study Completion Date: 2020-07-31

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.

Conditions

Chronic Pain Following Thermal Burn Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

n-3 PUFA (O3FA) + Vitamin D3

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

Group Type: EXPERIMENTAL

Omega-3 fatty acids (fish oil)

Intervention Type: 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

Vitamin D3 (cholecalciferol)

Intervention Type: DRUG

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

n-3 PUFA (O3FA) Placebo + Vitamin D3

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

Group Type: EXPERIMENTAL

Vitamin D3 (cholecalciferol)

Intervention Type: DRUG

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

Omega-3 fatty acid placebo

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Omega-3 fatty acids (fish oil)

Intervention Type: 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

Vitamin D3 (cholecalciferol) placebo

Intervention Type: DRUG

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

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

Group Type: PLACEBO_COMPARATOR

Vitamin D3 (cholecalciferol) placebo

Intervention Type: DRUG

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

Omega-3 fatty acid placebo

Intervention Type: DRUG

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

Interventions

Omega-3 fatty acids (fish oil)

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

Intervention Type: DRUG

Vitamin D3 (cholecalciferol)

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

Intervention Type: DRUG

Vitamin D3 (cholecalciferol) placebo

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

Intervention Type: DRUG

Omega-3 fatty acid placebo

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

Intervention Type: DRUG

Other Intervention Names

Fish oil; n-3 fatty acids; Cholecalciferol; Vitamin D3; Placebo, inert white powder; Vitamin D3 Matching Placebo; Placebo, corn/soy oil soft gels; PUFA Matching Placebo

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew C Mauck, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University Of North Carolina

Chapel Hill, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

17-1971

Identifier Type: -

Identifier Source: org_study_id