Clinical trial NCT00216970: Study of Arginine Metabolism and Nitric Oxide Formation in Relation to Glutamine Supply in Severely Burned Patients
Official title: Study of Arginine Metabolism and Nitric Oxide Formation in Relation to Glutamine Supply in Severely Burned Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Burns
Keywords: parenteral nutrition
burn injury
stable isotopes
Arginine Metabolic Kinetics
Nitric Oxide Formation
Glutamine Metabolic Kinetics
Lead sponsor: National Institute of General Medical Sciences (NIGMS)
Sponsor class: NIH
Collaborators: name: National Institutes of Health (NIH)
First posted: 2005-09-22
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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:

1. 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.
2. 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.
3. To estimate the rate of nitric oxide (NO) formation in burn patients using arginine and citrulline tracers

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 18 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: MGH Burn Unit
state: Massachusetts
Study officials:
affiliation: MGH, Shriner's Burn Hospital -Boston
name: Ronald G. Tompkins, MD, ScD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tharakan JF, Yu YM, Zurakowski D, Roth RM, Young VR, Castillo L. Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet. Clin Nutr. 2008 Aug;27(4):513-22. doi: 10.1016/j.clnu.2008.04.014. Epub 2008 Jun 30.
citation: Yu YM, Ryan CM, Castillo L, Lu XM, Beaumier L, Tompkins RG, Young VR. Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal. Am J Physiol Endocrinol Metab. 2001 Mar;280(3):E509-17. doi: 10.1152/ajpendo.2001.280.3.E509.
citation: Yu YM, Ryan CM, Burke JF, Tompkins RG, Young VR. Relations among arginine, citrulline, ornithine, and leucine kinetics in adult burn patients. Am J Clin Nutr. 1995 Nov;62(5):960-8. doi: 10.1093/ajcn/62.5.960.
citation: Castillo L, DeRojas-Walker T, Yu YM, Sanchez M, Chapman TE, Shannon D, Tannenbaum S, Burke JF, Young VR. Whole body arginine metabolism and nitric oxide synthesis in newborns with persistent pulmonary hypertension. Pediatr Res. 1995 Jul;38(1):17-24. doi: 10.1203/00006450-199507000-00004.
citation: Yu YM, Young VR, Castillo L, Chapman TE, Tompkins RG, Ryan CM, Burke JF. Plasma arginine and leucine kinetics and urea production rates in burn patients. Metabolism. 1995 May;44(5):659-66. doi: 10.1016/0026-0495(95)90125-6.