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

Burns Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00216970
• Other study ID #: 1999-P-008460
• Secondary ID: 5P50GM021700-28
• Status: Recruiting
• Phase: N/A
• First received: September 16, 2005
• Last updated: August 12, 2009
• Start date: August 1997
• Est. completion date: December 2009

Study information

• Verified date: August 2009
• Source: National Institute of General Medical Sciences (NIGMS)
• Contact: Mary-Liz C Bilodeau, MS
• Phone: 617-726-8766
• Email: mbilodeau[@]partners.org
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Burns

Intervention

Dietary Supplement:
• Alteration in nutritional support
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.

Locations

Country	Name	City	State
United States	MGH Burn Unit	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No

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