Supplemental Enteral Protein in Critical Illness

Protein-enhanced Enteral Nutrition and Metabolomics in Critically Ill Trauma and Surgical Patients

The aim of this study is too determine the effect of enteral protein supplementation on biochemical measures of inflammation and protein metabolism in critically ill surgical patients. The investigators will also collect data on important clinical outcomes, including infectious complications, duration of mechanical ventilation and other measures of recovery from critical illness.

Hypothesis: That early supplemental protein will increase serum concentrations of transthyretin at three weeks after the onset of illness or injury. Secondarily, the investigators will test whether supplementation, reduces infectious complications and increases ventilator-free days.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Trauma; Nutrition Disorder
• Intervention / Treatment: Other: Standard enteral nutrition; Dietary supplement: Protein supplementation

Detailed Description

Critically ill patients are frequently undernourished. The investigator's observations indicate that surgical and trauma patients who require artificial nutrition are likely to be markedly undernourished during the first week of critical illness, will often require intensive and costly support for organ failure, have prolonged stays in the intensive care unit and extended hospitalizations. Nitrogen deficits are typically greater and receive less attention than caloric deficits. In some respects, the focus on avoiding caloric deficits may have missed the mark. A broader consideration of nutrient needs, such as protein, is required. For instance, there are observational data supporting the notion that protein intake is at least as important as caloric intake in promoting recovery in critical illness. Only recently have national guidelines (ASPEN 2016) begun to specifically address protein requirements (1.5 - 2.0 g/kg/day). For a number of years, the approach to these critically ill patients has included weekly measurements of 24 hour urine nitrogen excretion in order to better understand the protein deficits that develop. Based upon physician preference, the investigators can then use enteral protein supplementation to match the urinary nitrogen excretion in order to achieve net "zero" nitrogen balance. With supplemental protein administration, physicians are able to reduce this deficit and in some cases, generate a positive nitrogen balance. However, there are no data to indicate that this approach (which is included as part of the 2016 ASPEN guidelines) improves clinical outcomes. The most obvious mechanism whereby supplemental protein may influence outcomes by providing more metabolic substrate for protein building. Feeding the gut likely creates a more anabolic environment and additional protein may facilitate anabolism. However, it is not known whether protein supplementation improves markers of anabolism and protein synthesis. In this study, the investigators will measure the anabolic effect of supplemental protein by following serum transthyretin concentrations as part of the standard clinical care.The investigators postulate that supplemental protein will attenuate the drop in comparison to no supplemental protein and will hasten the return to normal concentrations.

The proposed study will test whether early, and standardized protein supplementation: (1) Increases protein delivery during the first 2 weeks after injury, (2) increases serum transthyretin concentrations at 3 weeks after injury (3) increases ventilator-free days.

Study aims:

The aim of this study is to determine the effect of enteral protein supplementation on biochemical measures of protein metabolism in critically ill surgical patients. The investigators will also collect data on important clinical outcomes, including infectious complications, duration of mechanical ventilation and other measures of recovery from critical illness. However, this study will not enroll a sufficient number of subjects to adequately test for differences in these clinical end-points.

Hypothesis: That early supplemental protein will, increase serum concentrations of transthyretin at three weeks after injury. Secondarily, the investigators will test whether supplementation reduces infectious complications and increases ventilator-free days.

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Critically ill adult trauma (blunt and penetrating) victims
• Other critically ill surgical patients
• enteral nutrition required during the first 96 hours after injury
• expected to require nutritional support for at least 1 week

Exclusion Criteria:

• Significant chronic organ failure,
• severe malnutrition pre-existing prior to ICU admission
• not expected to survive from their traumatic injuries.
• intestinal discontinuity
• short bowel syndrome
• bowel obstruction
• enterocutaneous fistula
• intestinal ischemia
• massive gastrointestinal hemorrhage
• inability to obtain enteral access.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: no protein supplementation; subjects receiving enteral nutrition without any protein supplementation	Other: Standard enteral nutrition; Standard enteral nutrition.
Experimental: protein supplementation; subjects receiving enteral nutrition with additional protein supplementation	Dietary supplement: Protein supplementation; enteral protein supplementation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentrations of Transthyretin at 3 Weeks After Injury.	Transthyretin is a circulating biomarker of nutritional status and protein synthesis.	3 weeks after admission for injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free Days.	Ventilator-free days will measured in the standard way and indicate the number of days a subject was alive and not receiving mechanical ventilation during the first 28 days.	Within 28 days following admission to hospital following injury.
Ventilator Associated Pneumonia.	Pneumonia diagnosed while the patient is receiving mechanical ventilation as recorded in the institutional administrative trauma registry and ICU quality assurance database.	At any point during the hospitalization.

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Grant O'Keefe, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: April 18, 2017
• First Submitted That Met QC Criteria: May 25, 2017
• First Posted (Actual): May 31, 2017

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Nutrition Disorders
• Other Study ID Numbers: STUDY00007918; 1R01GM127790-01A1 (U.S. NIH Grant/Contract)

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