Study of Arginine Metabolism and Nitric Oxide Formation in Relation to Glutamine Supply in Severely Burned Patients

Study Overview
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Brief Summary
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The purpose of the study is to understand the way the body uses amino acids and proteins in burned patient during the time they cannot eat normally. This study aims to understand the metabolism of the amino acid arginine in the body after burn injury. The results of this study will help determine the best composition of food needed during an acute burn injury so that body can more efficiently use the supplied nutrient for optimal burn wound healing and early recovery.

Detailed Description
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The principle sources of plasma free arginine are (i) diet, (ii) release from protein breakdown and (iii) de novo synthesis directly from citrulline and the recycling of orthinine via the urea cycle. The major pathway of arginine disposal is i)oxidation via orthinine glutamate and subsequently the Tricarboxylic Acid (TCA) cycle and ii)via formation of nitric oxide. The latter pathway plays an important regulatory role in the body's response to stress and is significantly increased after burn injury. Previous studies with burn patients show i)an increased rate of total arginine flux, ii)a limited rate of arginine de novo synthesis, and iii) an apparent increase in the rate of arginine catabolism as measured indirectly by increased orinthine oxidation. These changes render arginine a conditionally essential amino acid for burn patients. Studies have shown that feeding glutamine to healthy adults significantly alters the blood concentrations of urea cycle intermediates arginine, citrulline and orthinine. Therefore, we hypothesize that the availability of arginine can be improved in the burn patient by supplementing total parenteral nutrition (TPN) support with glutamine. Using stable isotope tracer studies our specific aims are: To explore the dynamic aspects of arginine and citrulline metabolism. There will be an emphasis on arginine disposal via oxidation and urea nitrogen formation via nitric oxide production. To explore the effect of a) depleting arginine and its immediate precursors proline and glutamine, and b)glutamine supplementation on the metabolic pathways of burn patients. To estimate the rate of nitric oxide (NO) formation in burn patients using arginine and citrulline tracers

Official Title
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Study of Arginine Metabolism and Nitric Oxide Formation in Relation to Glutamine Supply in Severely Burned Patients

Conditions
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Burns

Intervention / Treatment
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* Dietary Supplement: Alteration in nutritional support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Burn patients being treated at MGH Burn Unit with one or more of the following criteria: 1) >=5% TBSA; 2) inhalation injury; or 3) resting energy expenditure (REE) of >15% of the predicted Basal Metabolic Rate using the Harris-Benedict equation. Must be receiving total parenteral nutrition in the course of their treatment. Exclusion Criteria: Patients with thyroid disease Patients who are not hemodynamically stable or show unstable vital signs Patients at the stage of major organ failure, e.g. renal and/or liver failure.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 1<br>Patients will receive nutritional support in which the contents of arginine = 0, glutamate = 0 and proline = 0. Stable isotope tracer studies will be conducted to investigate the whole body protein metabolism and the utilization of arginine in critically ill burn patients. | Dietary Supplement: Alteration in nutritional support<br>* The subject is randomized into one of two groups - One receives TPN that does not have arginine, proline or glutamate. The other will receive TPN with extra glutamine. The subject takes part in 3 tracer studies while in the hospital. For each tracer study, the subject will receive a different randomly assigned diet. Blood and air are sampled and the patient receives a stable isotope after which the tests are repeated.<br>* Other names: Nutritional Evaluation;|
| No Intervention: 2<br>In arm 2 patients will receive nutritional support which will provide glutamine 0.5g/kg/day. Stable isotope tracer studies will be conducted to investigate the whole body protein metabolism and the utilization of arginine in critically ill burn patients. | Dietary Supplement: Alteration in nutritional support<br>* The subject is randomized into one of two groups - One receives TPN that does not have arginine, proline or glutamate. The other will receive TPN with extra glutamine. The subject takes part in 3 tracer studies while in the hospital. For each tracer study, the subject will receive a different randomly assigned diet. Blood and air are sampled and the patient receives a stable isotope after which the tests are repeated.<br>* Other names: Nutritional Evaluation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This is a nutritional study. The primary outcome is to measure the protein kinetics of amino acid metabolism. Fate will be determine from measurements of subject blood and air samples. |  | 18 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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parenteral nutrition, burn injury, stable isotopes, Arginine Metabolic Kinetics, Nitric Oxide Formation, Glutamine Metabolic Kinetics