Feeding the Critically Ill During Phases of Altered Redox Status

NCT03085615 | Completed DMC

• 1 other identifier: FEDOX
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Thyroid Stimulating Hormone (TSH)

  7 days

• Triiodothyronine (T3)

  7 days

• Thyroxine (T4)

  7 days

• Reverse Triiodothyronine (rT3)

  7 days

Study Arms (2)

100%NRG

EXPERIMENTAL

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

40%NRG

ACTIVE COMPARATOR

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

Interventions

Jevity 1.5 OTHER

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

100%NRG; 40%NRG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• American Society for Parenteral and Enteral Nutrition: collaborator
• Rush University Medical Center: collaborator

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (2)

• 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.

  PMID: 31995239 DERIVED

• 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.

  PMID: 31581295 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Euthyroid Sick Syndromes; Systemic Inflammatory Response Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Thyroid Diseases; Endocrine System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Liam B McKeever, MS, PhD(c)

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

• Carol A Braunschweig, PhD

  Uinversity of Illinois at Chicago

  STUDY DIRECTOR

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Only our lab technicians will be truly blinding to group allocation.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Subjects will be randomized to receive either 25-30 kcals/kg or 12-14 kcals/kg. They will be followed for a maximum of 7 days or until ICU discharge. Blood draws will occur twice daily.

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 21, 2017
• Study Start: March 15, 2017
• Primary Completion: June 4, 2018
• Study Completion: October 13, 2018
• Last Updated: April 16, 2019

Record last verified: 2019-04

Locations

US (1)