BurnsNCT00216970
Study of Arginine Metabolism and Nitric Oxide Formation in Relation to Glutamine Supply in Severely Burned Patients
A study testing Alteration in nutritional support in people with Burns, run by Massachusetts General Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Burns
- What is being tested?
- Alteration in nutritional support
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 1997to Dec 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Yong-Ming Yu, MD, PhD contact
United States1 site, 1 recruiting
- Recruiting
MGH Burn Unit
Boston, Massachusetts, 02114
Colleen M
Colleen M Ryan, MD
About this study
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.
Read the 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:
- 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
- Conditions
- Burns
- Being tested
- Alteration in nutritional support
- Keywords
- parenteral nutrition, burn injury, stable isotopes, Arginine Metabolic Kinetics, Nitric Oxide Formation, Glutamine Metabolic Kinetics
- Medical subject headings
- Burns, Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alteration in nutritional supportDietary supplement
Also called Dietary Supplement, Nutritional Evaluation
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | 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. Receives: Dietary Supplement: Alteration in nutritional support |
| 2 | No intervention | 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. Receives: Dietary Supplement: Alteration in nutritional support |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startAug 1997
- Primary completionDec 2009 (estimated)
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for BurnsStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Investigators
- Ronald G. Tompkins, MD, ScD, Principal investigator, MGH, Shriner's Burn Hospital -Boston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00216970
- Sponsor's protocol ID
- 1999-P-008460
- Other IDs
- 5P50GM021700-28
- Status last verified
- Aug 2009
- First submitted
- 16 Sep 2005
- Last updated
- 13 Aug 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 18590940Yu 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.
PubMed 11171607Yu 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.
PubMed 7572742Castillo 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.
PubMed 7478791Yu 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.
PubMed 7752916
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Arginine Metabolism and Nitric Oxide Formation in Relation to Glutamine Supply in Severely Burned Patients
- ClinicalTrials.gov ID
- NCT00216970
- Acronym / sponsor ID
- 1999-P-008460
- Conditions
- Burns
- Keywords
- parenteral nutrition, burn injury, stable isotopes, Arginine Metabolic Kinetics, Nitric Oxide Formation, Glutamine Metabolic Kinetics
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Aug 1997
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Dec 2009 (estimated)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | Dietary Supplement: Alteration in nutritional supportPatients 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. |
| 2 | No intervention | Dietary Supplement: Alteration in nutritional supportIn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alteration in nutritional supportAlso: Dietary Supplement, Nutritional EvaluationThe 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. | Dietary supplement | 1, 2 |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2009.
- Background: PubMed 18590940Tharakan 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.
- Background: PubMed 11171607Yu 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.
- Background: PubMed 7572742Yu 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.
- Background: PubMed 7478791Castillo 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.
- Background: PubMed 7752916Yu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yong-Ming Yu, MD, PhD contact
Ronald G. Tompkins, MD, ScD principal investigator
MGH, Shriner's Burn Hospital -Boston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Alteration in nutritional support in people with Burns, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Aug 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mary-Liz C Bilodeau, MS (617-726-8766, mbilodeau@partners.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 18 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00216970, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2009.