Early and Adequate Protein Feeding Post-Traumatic Injury (EMS)

Early Metabolomic Support Study

A randomized, parallel-group, pilot study comparing the effect of the early addition of intravenous protein to enteral feeding as tolerated versus enteral feedings as tolerated alone immediately post traumatic injury.

Primary: To determine that early and adequate nutritional support will improve protein economy in the first week post -injury as measured by nitrogen balance. We hypothesize that an improvement in nitrogen balance with early maximized protein intake will support the production of acute phase proteins, major antioxidants and the inflammatory response.

Secondary: Through the use of mass spectrometry (MS) and nuclear magnetic resonance (NMR) technologies we will determine that our plan for early and adequate nutritional support with adequate protein from day one post injury will alter the metabolomics profile when compared to routine nutritional support.

Tertiary: For Specific Aim 3 we will measure several pro- and anti-inflammatory cytokines and soluble proteins.

Study Overview

• Status: Completed
• Conditions: Protein Feeding in Post-traumatic Injury Patients
• Intervention / Treatment: Drug: Routine Nutritional Support plus supplemental IV amino acids; Other: Routine Nutritional Support

Detailed Description

• Subjects admitted to the trauma service and cared for in the SICU will be screened for participation in this study.
• If subjects meet eligibility criteria, they will be enrolled and randomized 1:1 to enteral nutrition alone or enteral nutrition plus Amino Acid (AA) infusions.
• Nutritional assessment will be completed.
• Various procedures/assessments will take place over the course of the trial.
• Subjects will be followed for 28 days or until discharged or disposition of status.

Potential subjects deemed eligible will be randomized by the REDCap Randomization Module and begin study interventions within the first 24 hours of admission to the Surgical Intensive Care Unit (SICU).

Subjects enrolled into the Control Arm will receive routine nutritional support (RNS). RNS for the purpose of this study is defined as:

• Nutrition delivered via the enteral route of administration;
• Enteral caloric goal of 60-80% of energy requirements;
• Enteral feedings to be initiated as soon as medically feasible;
• Full parenteral nutrition to be initiated on Day 7 if enteral nutrition has not been started. Subjects will complete the study after Day 5 and will continue with nutritional support as clinically indicated.

Subjects enrolled into the Experimental Arm will receive RNS plus supplemental intravenous amino acids (RNS+IVAA). RNS+IVAA for the purpose of this study is defined as:

• Nutrition delivered via the enteral route of administration;
• Enteral caloric goal of 60-80% of energy requirements;
• Enteral feedings to be initiated as soon as medically feasible;
• Full parenteral nutrition to be initiated on Day 7 if enteral nutrition has not been started.
• Supplemental intravenous amino acids to begin within 24 hours of admission to the Surgical Intensive Care Unit (SICU);
• Amino acids to supplement enteral protein for total protein intake of approximately 1.5-2g/kg/day. Subjects will complete the study after Day 5 and will continue with nutritional support as clinically indicated.

Allocation of Treatment and Randomization Procedures 40 subjects will be recruited into the study and will be randomized in a 1:1 ratio. This will take place in lots of 10; permitting evaluation of data after every ten subjects. Potential subjects deemed eligible will be randomized in a blinded fashion by the REDCap Randomization Module to receive either routine nutritional support , enteral feedings as soon as medically feasible supplemented with intravenous amino acids " or routine nutritional support enteral feedings as soon as medically feasible. Randomization treatment assignment list will be created by our statistician; taking into consideration drop outs and replacements.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Trauma Patient /Male or female, any race/ethnicity
• Expected to survive 72 hours
• Admitted to the SICU
• Expected to remain in the hospital for at least 7 days
• Candidates for enteral nutrition post-injury

Exclusion Criteria:

• BMI less than 18 mg/m2 or greater than 35 mg/m2
• Immunosuppressive disorders (i.e. Prednisone >20mg daily; Organ Transplant Recipient with active immunosuppression treatments, diagnosis of HIV/AIDS).
• Type I or Type II Diabetes
• Pregnancy
• Pre-existing renal dysfunction (creatinine >2.5mg/dL).
• Clear contraindication for enteral nutrition immediately post injury
• Severe liver dysfunction (Total Bilirubin > 3.0mg%)
• Non-English speaking patients
• Known allergies to any of the study drug's components

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental Group; Routine Nutritional Support plus supplemental IV amino acids, to begin within 24h of injury. (Target approximately 1.5-2g protein/kg/day)	Drug: Routine Nutritional Support plus supplemental IV amino acids; Enteral nutrition as tolerated Plus supplemental IV AA infusion to meet the target of approximately 1.5-2.0gm protein/kg/day total starting within 24 hours of injury for 5 days.; Other Names: Plenamine
ACTIVE_COMPARATOR: Control Group; Routine Nutritional Support (i.e. enteral nutrition as tolerated, to begin as early as medically feasible)	Other: Routine Nutritional Support; Enteral nutrition as tolerated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitrogen balance and Catabolic Index	We will use the urine specimen collections to measure nitrogen balance and catabolic index, both of which assess the level of physiologic stress. A catabolic Index less than zero represents no significant stress, an index greater than or equal to zero and less than or equal to 5 represents moderate stress, and an index greater than 5 represents severe stress. Twenty-four hour urine collections will be done for measurement of urine urea nitrogen to estimate nitrogen balance on day 1 and day 5 or 6 or 7 of the study. This will allow us to compare degree of catabolism and nitrogen efficiency between groups as well as between the two time points (Day 1 and Day 5 or 6 or 7). We hypothesize the early and adequate protein feeding group, although receiving fewer overall calories than subjects' total requirements, will have less negative nitrogen balance than the control group.	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomics Profiles	Through the use of mass spectrometry (MS) and nuclear magnetic resonance (NMR) technologies we will determine whether our plan for early and adequate nutritional support with adequate protein from day one post injury will alter the metabolomics profile when compared to routine nutritional support. We expect: An improvement in protein (specifically branched chain amino acid) utilization with reduced 3-methylhistidine production and decreased proteolysis from peripheral stores;; Improved redox potential as measured by products of oxidation: primarily glutathione precursors and metabolites and products of lipid peroxidation;; Improvement in the lipid milieu seen post injury to reflect expected inflammatory response and not reflect the metabolomics profile observed with developing MODS (i.e. increased glycerol heads of phospholipids as opposed to increased fatty acyl chain, creatinine and lactate).	8 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Biomarkers	Early and adequate protein support will modify the levels of select pro and anti-inflammatory cytokines levels as compared to standard nutritional care. We anticipate decreased levels of the stress response mediators such as cortisol, Tumor Necrosis Factor (TNF), Interleukin-6 (IL-8)and Interleukin-8 (IL-8). These inflammatory markers are also key regulators of the breakdown of muscle during the acute stress response and their down-regulation would also serve to protect lean muscle mass.	8 days

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Peter A Burke, MD, Boston Medical Center

Publications and helpful links

General Publications

• Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011 Aug 11;365(6):506-17. doi: 10.1056/NEJMoa1102662. Epub 2011 Jun 29.
• Hill AA, Plank LD, Finn PJ, Whalley GA, Sharpe N, Clark MA, Hill GL. Massive nitrogen loss in critical surgical illness: effect on cardiac mass and function. Ann Surg. 1997 Aug;226(2):191-7. doi: 10.1097/00000658-199708000-00011.
• Sandstrom R, Drott C, Hyltander A, Arfvidsson B, Schersten T, Wickstrom I, Lundholm K. The effect of postoperative intravenous feeding (TPN) on outcome following major surgery evaluated in a randomized study. Ann Surg. 1993 Feb;217(2):185-95. doi: 10.1097/00000658-199302000-00013.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 7, 2017
• Primary Completion (ACTUAL): October 18, 2019
• Study Completion (ACTUAL): October 18, 2019

Study Registration Dates

• First Submitted: June 29, 2016
• First Submitted That Met QC Criteria: July 15, 2016
• First Posted (ESTIMATE): July 20, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Nutritional Support; Metabolic Support; Neuro-endocrine Event; Enteral feedings; Parenteral feeding
• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: H-34322; 1R21DK108145-01A1 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: A Data and Safety Monitoring Safety plan has been created per Boston University Medical Campus (BUMC) guidelines. The Principal Investigator at Boston Medical Center (BMC) or Boston University Medical Campus will report all adverse events and Unanticipated Problems to the Institutional Review Board (IRB) in compliance with IRB policy, Federal/State regulations, and sponsor requirements.

Drug and device information, study documents

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