Feeding the Critically Ill During Phases of Altered Redox Status
American Society for Parenteral and Enteral Nutrition
University of Illinois at Chicago

      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.
    
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