BurnsNCT00216983
Proline Metabolism in Severely Burned Patients: Effect of Modulated Parenteral Feeding
An observational study of Burns, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The overall purpose of the study is to evaluate the effect of depleting proline supply in the nutritional support regimen on proline metabolism in the burn patients, this includes the rate of proline oxidation after burn injury, the rate of proline de novo synthesis from its immediate precursors glutamate and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Burns
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 1997to Jan 2010
- Phase
- Observational
- 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
Study population: Critically ill burn patients
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.
United States1 site
Massachusetts General Hospital Burn Unit
Boston, Massachusetts, 02114
About this study
Official title: Proline Metabolism in Severely Burned Patients: Effect of Modulated Parenteral Feeding.
The overall purpose of the study is to evaluate the effect of depleting proline supply in the nutritional support regimen on proline metabolism in the burn patients, this includes the rate of proline oxidation after burn injury, the rate of proline de novo synthesis from its immediate precursors glutamate and ornithine. The specific aims of the proposed study are: 1) to determine the kinetic status of proline metabolism and whole body proline balance under the following nutritional states: (a) "fasting; (b) regular total parenteral nutrition (TPN); (c)TPN with isonitrogenous depletion of proline, glutamate and ornithine metabolism under nutritional conditions studied in specific aim 1) above.
Read the detailed description
Proline is a non-essential amino acid. Its synthesis and catabolism is via the pathway of ornithine and glutamate, the latter two amino acids serve as its immediate precursors as well as metabolites. Ornithine is one of the intermediates for urea cycle, and glutamate is metabolically connected to tricarboxylic acid (TCA) cycle, the major cycle for energy production.
It is hypothesized that the significantly increased rates of net nitrogen loss and energy "production", as the consequence of the accelerated activities of both the urea and TCA cycles in burn injury "drain" both ornithine and glutamate, thus depleting tissues of the availability of proline. Hence, the de novo synthesis of proline is likely to be affected by the reduced availability of its major precursors: glutamate and ornithine.
This hypothesis is supported by 1) tissue and circulating glutamine content are reduced in stressed conditions; 2) ornithine disposal via oxidation is significantly increased after burn injury(2). Therefore, the availability of proline is likely to be limiting after burn injury for the synthesis of proteins. On the other hand, proline requirement is significantly increased in burn patients due to the high demand for tissue repair and wound healing. As a result, providing an adequate proportion of its precursors, glutamine / glutamate and / or as preformed proline, is of importance to maintain the appropriate supply and balance of amino acids for protein and other synthetic functions after burn injury.
The overall purpose of the study is to evaluate the effect of depleting proline supply in the nutritional support regimen on proline metabolism in the burn patients, this includes the rate of proline oxidation after burn injury, the rate of proline de novo synthesis from its immediate precursors glutamate and ornithine. The specific aims of the proposed study are: 1) to determine the kinetic status of proline metabolism and whole body proline balance under the following nutritional states: (a) "fasting; (b) regular total parenteral nutrition (TPN); (c)TPN with isonitrogenous depletion of proline, glutamate and ornithine metabolism under nutritional conditions studied in specific aim 1) above.
- Conditions
- Burns
- Keywords
- parenteral nutrition, burn injury, stable isotopes, Proline Metabolic Kinetics, Ornithine Metabolic Kinetics, Glutamate Metabolic Kinetics, 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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Fasting condition to measure: 1. quantitative relationships among proline, ornithine and glutamate with an emphasis on evaluating the rate of proline disposal and its conversion to ornithine and glutamate in burn patients 2. Evaluating the rate of proline de novo synthesis from glutamate or ornithine in burn patients | |
| 2 | We will study the quantitative relationships among proline, ornithine and glutamate with an emphasis on evaluating the rate of proline disposal and its conversion to ornithine and glutamate in burn patients. When the patients are receiving regular TPN or TPN depleted with proline - arginine - glutamate. | |
| 3 | We wull evaluate the rate of proline de novo synthesis from glutamate or ornithine in burn patients when the patients are receiving regular TPN or TPN depleted proline-arginine-glutamate. |
What is being measured
The primary outcome is the main question the study is designed to answer.
This is a study for measuring the protein kinetics for metabolism of the amino acid proline kinetics will be derived from measurements on blood and air samples taken as part of the study.
Measured: 12 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 startSep 1997
- Primary completionJan 2010 (estimated)
- Study completionJan 2010 (estimated)
Why it stopped: State of Mass. tightened regulations for making intravenous solutions for research subjects. Study was withdrawn and no participants were enrolled.
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
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
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, Shriners Burn Hospital - Boston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00216983
- Sponsor's protocol ID
- 1999-P-008463
- Other IDs
- 2P50GM021700-27
- Status last verified
- Jan 2017
- First submitted
- 20 Sep 2005
- Last updated
- 13 Jan 2017
- 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 7572742Jaksic T, Wagner DA, Burke JF, Young VR. Proline metabolism in adult male burned patients and healthy control subjects. Am J Clin Nutr. 1991 Aug;54(2):408-13. doi: 10.1093/ajcn/54.2.408.
PubMed 1858705Jaksic T, Wagner DA, Burke JF, Young VR. Plasma proline kinetics and the regulation of proline synthesis in man. Metabolism. 1987 Nov;36(11):1040-6. doi: 10.1016/0026-0495(87)90023-0.
PubMed 3670073
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proline Metabolism in Severely Burned Patients: Effect of Modulated Parenteral Feeding.
- ClinicalTrials.gov ID
- NCT00216983
- Acronym / sponsor ID
- 1999-P-008463
- Conditions
- Burns
- Keywords
- parenteral nutrition, burn injury, stable isotopes, Proline Metabolic Kinetics, Ornithine Metabolic Kinetics, Glutamate Metabolic Kinetics, Glutamine Metabolic Kinetics
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: State of Mass. tightened regulations for making intravenous solutions for research subjects. Study was withdrawn and no participants were enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Sep 1997
- Primary completion
- Jan 2010 (estimated)
- Study completion
- Jan 2010 (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 overall purpose of the study is to evaluate the effect of depleting proline supply in the nutritional support regimen on proline metabolism in the burn patients, this includes the rate of proline oxidation after burn injury, the rate of proline de novo synthesis from its immediate precursors glutamate and ornithine. The specific aims of the proposed study are: 1) to determine the kinetic status of proline metabolism and whole body proline balance under the following nutritional states: (a) "fasting; (b) regular total parenteral nutrition (TPN); (c)TPN with isonitrogenous depletion of proline, glutamate and ornithine metabolism under nutritional conditions studied in specific aim 1) above.
Detailed description
Proline is a non-essential amino acid. Its synthesis and catabolism is via the pathway of ornithine and glutamate, the latter two amino acids serve as its immediate precursors as well as metabolites. Ornithine is one of the intermediates for urea cycle, and glutamate is metabolically connected to tricarboxylic acid (TCA) cycle, the major cycle for energy production.
It is hypothesized that the significantly increased rates of net nitrogen loss and energy "production", as the consequence of the accelerated activities of both the urea and TCA cycles in burn injury "drain" both ornithine and glutamate, thus depleting tissues of the availability of proline. Hence, the de novo synthesis of proline is likely to be affected by the reduced availability of its major precursors: glutamate and ornithine.
This hypothesis is supported by 1) tissue and circulating glutamine content are reduced in stressed conditions; 2) ornithine disposal via oxidation is significantly increased after burn injury(2). Therefore, the availability of proline is likely to be limiting after burn injury for the synthesis of proteins. On the other hand, proline requirement is significantly increased in burn patients due to the high demand for tissue repair and wound healing. As a result, providing an adequate proportion of its precursors, glutamine / glutamate and / or as preformed proline, is of importance to maintain the appropriate supply and balance of amino acids for protein and other synthetic functions after burn injury.
The overall purpose of the study is to evaluate the effect of depleting proline supply in the nutritional support regimen on proline metabolism in the burn patients, this includes the rate of proline oxidation after burn injury, the rate of proline de novo synthesis from its immediate precursors glutamate and ornithine. The specific aims of the proposed study are: 1) to determine the kinetic status of proline metabolism and whole body proline balance under the following nutritional states: (a) "fasting; (b) regular total parenteral nutrition (TPN); (c)TPN with isonitrogenous depletion of proline, glutamate and ornithine metabolism under nutritional conditions studied in specific aim 1) above.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Fasting condition to measure: 1. quantitative relationships among proline, ornithine and glutamate with an emphasis on evaluating the rate of proline disposal and its conversion to ornithine and glutamate in burn patients 2. Evaluating the rate of proline de novo synthesis from glutamate or ornithine in burn patients |
| 2 | – | –We will study the quantitative relationships among proline, ornithine and glutamate with an emphasis on evaluating the rate of proline disposal and its conversion to ornithine and glutamate in burn patients. When the patients are receiving regular TPN or TPN depleted with proline - arginine - glutamate. |
| 3 | – | –We wull evaluate the rate of proline de novo synthesis from glutamate or ornithine in burn patients when the patients are receiving regular TPN or TPN depleted proline-arginine-glutamate. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Critically ill burn patients
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 (1 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.
Primary outcome
This is a study for measuring the protein kinetics for metabolism of the amino acid proline kinetics will be derived from measurements on blood and air samples taken as part of the study.
Time frame: 12 hours
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2017.
- 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 1858705Jaksic T, Wagner DA, Burke JF, Young VR. Proline metabolism in adult male burned patients and healthy control subjects. Am J Clin Nutr. 1991 Aug;54(2):408-13. doi: 10.1093/ajcn/54.2.408.
- Background: PubMed 3670073Jaksic T, Wagner DA, Burke JF, Young VR. Plasma proline kinetics and the regulation of proline synthesis in man. Metabolism. 1987 Nov;36(11):1040-6. doi: 10.1016/0026-0495(87)90023-0.
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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.
Ronald G Tompkins, MD, ScD principal investigator
MGH, Shriners Burn Hospital - Boston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of 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 1 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: withdrawn, as of the sponsor's last update on 13 Jan 2017. 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
This is a study for measuring the protein kinetics for metabolism of the amino acid proline kinetics will be derived from measurements on blood and air samples taken as part of the study. (time frame: 12 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 NCT00216983, 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 Jan 2017.