Feeding the Critically Ill During Phases of Altered Redox Status (FEDOX)

Feeding the Critically Ill During Phases of Altered Redox Status (FEDOX): a Prospective Randomized Trial

The FEDOX trial is a prospective randomized clinical trial exploring oxidative stress as a mechanism of harm to explain the negative outcomes found in feeding trials that achieved caloric exposure commensurate with the nationally recommended guidelines. Due to its impact on energy metabolism, we will also explore low T3 syndrome's relationship to this mechanism. Finally, we will explore circadian patterns of diurnal/nocturnal TSH fluctuation as a potential biomarker to indicate this mechanism of harm has subsided.

This 7-day prospective randomized clinical trial is designed to address the following specific aims (SA) in ICU patients (n=40) with systemic inflammatory response syndrome.

SA1) Determine whether provision of enteral nutrition (EN) at 100% of levels in Nationally Recommended Guidelines NRG (25-30 kcals/kg, 100%NRG) early in critical illness increases reactive oxygen species (ROS) production compared to EN at 40% of NRG levels (10-12 kcals/kg, 40%NRG). Subjects will be fasted overnight and randomized to receive either 100% NRG or 40%NRG for 7 days. Plasma F2-isoprostanes will be measured daily and compared between groups through repeated measures analysis.

SA2) Determine if EN at 100%NRG interrupts the critical illness induced low T3 syndrome and subsequently further increases the ROS production compared to 40%NRG. Serum thyroid parameters (T3, T4, rT3, TSH) with be measured daily and compared between groups as above.

Mediation analysis will be used to determine the proportion of the effect of nutrition group on F2-isoprostane production explained by each thyroid parameter.

SA3) Determine if the return of diurnal/noctural fluctuations in TSH is associated with decreased nutrition-induced ROS production. Plasma TSH will be measured twice per day at 0300 and 1800hrs to determine TSH fluctuation. The interaction effect between TSH fluctuation and nutrition group on F2-isoprostane production will be assessed through repeated measures analysis. This study provides vital mechanistic insight into the impact of feeding on oxidative stress during the first week of critical illness, represents an important first step in determining the safest timing and dosage of nutrition support, and sets the foundation for future larger clinical trials on these topics.

Study Overview

• Status: Completed
• Conditions: Systemic Inflammatory Response Syndrome; Oxidative Stress; Acute Respiratory Distress Syndrome; Euthyroid Sick Syndromes
• Intervention / Treatment: Other: Jevity 1.5

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (>18 years) admitted to RUMC MICU who are able to receive EN, who have two consecutive white blood cell lab values above 12,000/mm^3 or below 4,000/mm^3 plus at least one of the following 3 criteria met for at the past 12 hours will be eligible for participation. Criteria: (1) a respiratory rate greater than 20 breaths per minute or PaCO2 less than 32mmHg, (2) a heart rate greater than 90 beats per minute, or (3) a temperature greater than 100.4F or less than 96.8F.

Exclusion Criteria: Patients will be excluded if the are pregnant, have documented neurologic disease prior to admission that interferes with the capacity to give informed consent or do not require EN for their nutritional care.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 100%NRG; Patient will receive the enteral nutrition product Jevity 1.5 starting at 20mL per hour and increasing by 20mL every four hours until a goal rate delivering 25-30kcals/kg is achieved. If feeding is interrupted, flow rate will be adjusted to compensate for nutritional loss.	Other: Jevity 1.5; Jevity 1.5 is an enteral nutrition product delivering 1.5 kcals/mL and 0.06 g protein/mL.
Active Comparator: 40%NRG; Patient will receive the enteral nutrition product Jevity 1.5 starting at 20mL per hour and increasing by 20mL every four hours until a goal rate delivering 12-14 kcals/kg is achieved. If feeding is interrupted, flow rate will be adjusted to compensate for nutritional loss.	Other: Jevity 1.5; Jevity 1.5 is an enteral nutrition product delivering 1.5 kcals/mL and 0.06 g protein/mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily Plasma F2-Isoprostane levels	Plasma maximum concentration of F2-isoprostanes will be quantified through liquid chromatography tandem mass spectrometry (LC-MS/MS) of plasma using a Q-trap mass spectrometer.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thyroid Stimulating Hormone (TSH)	TSH will be measured twice per day using commercially available immuno-assay kits.	7 days
Triiodothyronine (T3)	T3 will be measured daily using commercially available immuno-assay kits.	7 days
Thyroxine (T4)	T4 will be measured daily using commercially available immuno-assay kits.	7 days
Reverse Triiodothyronine (rT3)	rT3 will be measured daily using commercially available immuno-assay kits.	7 days

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: Rush University Medical Center; American Society for Parenteral and Enteral Nutrition
• Investigators: Principal Investigator: Liam B McKeever, MS, PhD(c), University of Illinois at Chicago; Study Director: Carol A Braunschweig, PhD, Uinversity of Illinois at Chicago; Study Chair: Omar Lateef, DO, Rush University Medical Center; Study Chair: Marcelo Bonini, PhD, University of Illinois at Chicago; Study Chair: Antonio Bianco, MD, PhD, Rush University Medical Center; Study Chair: Sarah J Peterson, PhD, Rush University Medical Center; Study Chair: Alan Diamond, PhD, University of Illinois at Chicago; Study Chair: Sally Freels, PhD, University of Illinois at Chicago

Publications and helpful links

General Publications

• McKeever L, Peterson SJ, Cienfuegos S, Rizzie J, Lateef O, Freels S, Braunschweig CA. Real-Time Energy Exposure Is Associated With Increased Oxidative Stress Among Feeding-Tolerant Critically Ill Patients: Results From the FEDOX Trial. JPEN J Parenter Enteral Nutr. 2020 Nov;44(8):1484-1491. doi: 10.1002/jpen.1776. Epub 2020 Jan 29.
• McKeever L, Peterson SJ, Lateef O, Freels S, Fonseca TL, Bocco BMLC, Fernandes GW, Roehl K, Nowak K, Mozer M, Bianco AC, Braunschweig CA. Higher Caloric Exposure in Critically Ill Patients Transiently Accelerates Thyroid Hormone Activation. J Clin Endocrinol Metab. 2020 Feb 1;105(2):523-33. doi: 10.1210/clinem/dgz077.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Actual): June 4, 2018
• Study Completion (Actual): October 13, 2018

Study Registration Dates

• First Submitted: March 15, 2017
• First Submitted That Met QC Criteria: March 15, 2017
• First Posted (Actual): March 21, 2017

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Inflammation; Endocrine System Diseases; Disease; Infant, Newborn, Diseases; Thyroid Diseases; Shock; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Systemic Inflammatory Response Syndrome; Euthyroid Sick Syndromes
• Other Study ID Numbers: FEDOX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No