Vitamin E Supplementation in Burn Patients

Burned patients because of their increased oxidative stress have severely depleted vitamin E, which is a dietary antioxidant. Oxidative stress is responsible for much of the pathophysiology seen in burned patients, which leads to acute and chronic morbidity and mortality, in addition to a decrease in their quality of life. Oral vitamin E will be used to reverse the oxidative stress of burn injury and, in the process, decrease the secondary consequences of thermal trauma. This proposal will demonstrate the benefit of maintaining adequate vitamin E status.

Study Overview

• Status: Withdrawn
• Conditions: Burn Injury
• Intervention / Treatment: Drug: dl-alpha-tocopheryl acetate

Detailed Description

We have previously demonstrated that thermal injury depletes plasma vitamin E in pediatric burn patients. However, plasma changes reflect short-term vitamin E changes, whereas adipose tissue alpha-tocopherol concentrations reflect long-term vitamin E status. We reported last year that burn injury depleted vitamin E stores in adipose tissue in children by nearly half within one month following injury. Our long-term goal is to improve the quality of life of burn patients by preventing pulmonary and hepatic dysfunction that may occur from vitamin E depletion. The objectives of this application are to a) attenuate alpha-tocopherol depletion in burned patients by vitamin E supplementation, b) prevent or reverse oxidative stress in these patients, and c) collect pilot data on the effect of vitamin E supplementation on lung and liver function. Our central hypothesis is that the administration of high doses of alpha-tocopherol will prevent or restore levels of vitamin E in adipose tissue and reverse the oxidative state in burned patients. The rationale of the proposed studies is that in severe cases of vitamin E depletion, oxidative stress, fatty liver and lung dysfunction have all been reported in our patients. We will administer vitamin E supplements (300-1200 IU RRR-alpha-tocopherol) to burn subjects (n= 20 per group, 6-70 years, ≥20% total body surface burns) for fifteen days. The subjects will be randomly assigned into two groups: an early treatment group who will receive vitamin E for days 1-15 of the study, and a delayed treatment group who will receive vitamin E for days 16-30 of the study. Both groups will be studied for a total of thirty days. We will test the following aims: Aim 1: determine the degree that supplemental Vitamin E will attenuate alpha-tocopherol depletion. Aim 2: determine if supplemental Vitamin E reduces markers of oxidative stress in burned patients. Aim 3: collect preliminary data to establish the relationship between oxidative stress and pulmonary pathophysiology and fatty liver after burn injury. We will measure plasma and adipose tissue alpha-tocopherol and urinary and plasma markers of oxidative stress, prior to supplementation and then weekly. The proposed research is innovative because the oxidative stress of burn injury causes a severe depletion of an essential nutrient, vitamin E. Supplementation of vitamin E is a novel concept that may mitigate the complications of burns, including lung injury, fatty liver and peripheral neuropathy.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555
      • Shriners Hospitals for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 85 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 6 months - 85 years
• >20% TBSA burn

Exclusion Criteria:

• Bleeding disorders
• Positive hepatitis or HIV screens
• Pregnancy (women)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin E Treated	Drug: dl-alpha-tocopheryl acetate; Ages 6 months-1 year will receive 75 IU/day of dl-alpha-tocopheryl acetate, while ages 2-5 years will receive 150 IU/day. Ages 6-8 will receive 300 IU/day, while ages 9-13 will receive 600 IU/day, ages 14-17 will receive 800 IU/day, and ages 18-70 will receive 1200 IU/day. Vitamin E will be administered in a liquid or pill form. The dose of aqueous vitamin E (Aqueous Vitamin E Oral Drops, Silarx, No. 54838-0005-30, Spring Valley, NY) will be given orally. When/If the patient is able to eat independently, the dose of vitamin E may be given in a pill form (Novatol 5-57, No. 410217, Archer Daniels Midland Company, Decatur, IL). Depending on the subject's group, the supplement of vitamin E either will be given on days 1-15 of the study or days 16-30 of the study.; Other Names: Vitamin E; Aqueous Vitamin E Oral Drops, Silarx, No. 54838-0005-30
No Intervention: Untreated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Alpha-Tocopherol in Plasma, Adipose (also: Lung, Skin, Muscle, Liver in the case of Death)	30 Days
Gamma-Tocopherol in Plasma, Adipose (also: Lung, Skin, Muscle, Liver in the case of Death)	30 Days
Vitamin E Metabolites in Plasma, Urine	30 Days
Malondialdehyde in Plasma, Urine (also: Lung, Skin, Muscle in the case of Death)	30 Days
Isoprostanes in Plasma, Urine (also: Lung, Skin, Muscle in the case of Death)	30 Days
Lipid Panel in Plasma and Triglyceride Concentration	30 Days
Liver Ultrasound	30 Days
Pulmonary Function Study Variables	30 Days
Cardiopulmonary Stress Test	30 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Open Body Surface Area and Wound Healing	30 Days
Weight	30 Days
Basal Metabolic Rate	30 Days
Diet History and Food Intake	30 Days
Fluid Balance	30 Days
Incidence of Acute Respiratory Distress Syndrome (ARDS)	30 Days
Incidence of Pneumonia	30 Days
Incidence of Atelectasis	30 Days
Ventilator Variables (Compliance, Resistance, Work of Breathing, Number of Days Ventilated)	30 Days
Pulmonary Status Variables (Spirometry, Blood Gas, Diffusion Constant, Pulmonary Capillary Surface Area)	30 Days

Collaborators and Investigators

• Sponsor: Shriners Hospitals for Children
• Collaborators: University of Texas; Oregon State University
• Investigators: Principal Investigator: Jong O Lee, MD, University of Texas Medical Branch, Shriners Hospitals for Children; Study Director: Hal K Hawkins, MD, PhD, University of Texas Medical Branch, Shriners Hospitals for Children; Study Director: Linda E Sousse, PhD, MBA, University of Texas Medical Branch, Shriners Hospitals for Children; Study Director: Daniel L Traber, PhD, University of Texas Medical Branch, Shriners Hospitals for Children; Study Director: Maret G Traber, PhD, Oregon State University; Study Director: David N Herndon, M.D., University of Texas Medical Branch, Shriners Hospitals for Children; Study Director: Celeste C Finnerty, Ph.D., University of Texas Medical Branch, Shriners Hospitals for Children

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): August 1, 2017
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: August 9, 2011
• First Submitted That Met QC Criteria: August 9, 2011
• First Posted (Estimate): August 10, 2011

Study Record Updates

• Last Update Posted (Actual): September 21, 2021
• Last Update Submitted That Met QC Criteria: September 20, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Vitamin E; Lung Dysfunction; Fatty Liver; Burn; Oxidation; Lipid Peroxidation
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Antioxidants; Vitamin E; Tocopherols; alpha-Tocopherol; Vitamins; Tocotrienols
• Other Study ID Numbers: VitE2011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No