Feeding the Critically Ill During Phases of Altered Redox Status

Summary

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.

Conditions

• Acute Respiratory Distress Syndrome
• Oxidative Stress
• Euthyroid Sick Syndromes
• Systemic Inflammatory Response Syndrome

Interventions

OTHER

Jevity 1.5

Jevity 1.5 is an enteral nutrition product delivering 1.5 kcals/mL and 0.06 g protein/mL.

Sponsors & Collaborators

• American Society for Parenteral and Enteral Nutrition

  collaborator OTHER

• Rush University Medical Center

  collaborator OTHER

• University of Illinois at Chicago

  lead OTHER

Principal Investigators

• Liam B McKeever, MS, PhD(c) · University of Illinois at Chicago

• Carol A Braunschweig, PhD · Uinversity of Illinois at Chicago

• Omar Lateef, DO · Rush University Medical Center

• Marcelo Bonini, PhD · University of Illinois at Chicago

• Antonio Bianco, MD, PhD · Rush University Medical Center

• Sarah J Peterson, PhD · Rush University Medical Center

• Alan Diamond, PhD · University of Illinois at Chicago

• Sally Freels, PhD · University of Illinois at Chicago

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-03-15

Primary Completion

2018-06-04

Completion

2018-10-13

Countries

• United States

Study Locations