EMS: Early and Adequate Protein Feeding Post-Traumatic Injury

Sponsor

Boston Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT02837861

Collaborator

National Institutes of Health (NIH) (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

31.4

Actual Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Protein Feeding in Post-traumatic Injury Patients	Drug: Routine Nutritional Support plus supplemental IV amino acids Other: Routine Nutritional Support	Early Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Early Metabolomic Support Study

Actual Study Start Date :

Mar 7, 2017

Actual Primary Completion Date :

Oct 18, 2019

Actual Study Completion Date :

Oct 18, 2019

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Nitrogen balance and Catabolic Index [8 days]
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.

Secondary Outcome Measures

Metabolomics Profiles [8 days]
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).

Other Outcome Measures

Inflammatory Biomarkers [8 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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