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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by National Institute of General Medical Sciences (NIGMS).
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
National Institute of General Medical Sciences (NIGMS)
ClinicalTrials.gov Identifier:
NCT00216970
First received: September 16, 2005
Last updated: August 12, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention
Burns
Dietary Supplement: Alteration in nutritional support

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of Arginine Metabolism and Nitric Oxide Formation in Relation to Glutamine Supply in Severely Burned Patients

Resource links provided by NLM:


Further study details as provided by National Institute of General Medical Sciences (NIGMS):

Primary Outcome Measures:
  • 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. [ Time Frame: 18 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: August 1997
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1

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
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.
Other Names:
  • Dietary Supplement
  • Nutritional Evaluation
No Intervention: 2
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
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.
Other Names:
  • Dietary Supplement
  • Nutritional Evaluation

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00216970

Contacts
Contact: Mary-Liz C Bilodeau, MS 617-726-8766 mbilodeau@partners.org
Contact: Yong-Ming Yu, MD, PhD

Locations
United States, Massachusetts
MGH Burn Unit Recruiting
Boston, Massachusetts, United States, 02114
Contact: Colleen M         
Sub-Investigator: Colleen M Ryan, MD         
Sub-Investigator: Shawn P Fagan, MD         
Sub-Investigator: Robert L Sheridan, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Ronald G. Tompkins, MD, ScD MGH, Shriner's Burn Hospital -Boston
  More Information

Additional Information:
Publications:
Responsible Party: Ronald G. Tompkins, MD, ScD, Chief, Burn Service, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00216970     History of Changes
Other Study ID Numbers: 1999-P-008460, 5 P50 GM021700-28
Study First Received: September 16, 2005
Last Updated: August 12, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute of General Medical Sciences (NIGMS):
parenteral nutrition
burn injury
stable isotopes
Arginine Metabolic Kinetics
Nitric Oxide Formation
Glutamine Metabolic Kinetics

Additional relevant MeSH terms:
Nitric Oxide
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 29, 2014