Early and Adequate Protein Feeding Post-Traumatic Injury

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Early Metabolomic Support Study

Conditions
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Protein Feeding in Post-traumatic Injury Patients

Intervention / Treatment
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* Drug: Routine Nutritional Support plus supplemental IV amino acids
* Other: Routine Nutritional Support


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>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<br>* 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.<br>* Other names: Plenamine;|
| Active Comparator: Control Group<br>Routine Nutritional Support (i.e. enteral nutrition as tolerated, to begin as early as medically feasible) | Other: Routine Nutritional Support<br>* Enteral nutrition as tolerated.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic Support, Nutritional Support, Neuro-endocrine Event, Enteral feedings, Parenteral feeding