Critical IllnessPhase 2/3NCT00318331
Enteral Glutamine in Critical Illness
A Phase 2/3 study testing Glutamine in people with Critical Illness and Sepsis, run by Christiana Care Health Services at 1 site in United States.
Trial summary
Glutamine is an amino acid which is rapidly depleted in critical illness. It is used as energy by cells that line the gut, vital for immune system function, and works as an anti-oxidant. Glutamine supplementation has been shown to improve outcomes in ICU patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Sepsis, Respiratory Insufficiency
- What is being tested?
- Glutamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- May 2006to Sep 2007
- Phase
- Phase 2/3
- 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
- Admission to MICU/ CICU
- Age greater than or equal to 18 years old
- Requirement for enteral nutrition
- Presence or planned insertion of central venous catheter as part of routine medical care
- Requirement for mechanical ventilation
- APACHE II Score >/= 15
Who cannot join
- Female of child-bearing age (i.e. less than 45 years old)
- Enteral nutrition begun prior to randomization
- Receiving Total Parenteral Nutrition
- Requirement for protein restriction
- Creatinine >4 mg/dl
- History of cirrhosis and/or clinical signs of heptic encephalopathy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Clinical Trial Comparing Enteral Glutamine Supplementation to Standard of Care Enteral Feeding in Critical Illness
Glutamine is an amino acid which is rapidly depleted in critical illness. It is used as energy by cells that line the gut, vital for immune system function, and works as an anti-oxidant. Glutamine supplementation has been shown to improve outcomes in ICU patients. We hypothesize that critically ill patients given extra glutamine will have less of an inflammatory response and therefore better outcomes than patients not given extra glutamine. Our study randomizes patients to tube feeding with OR without extra glutamine to see if it affects patient outcomes as well as markers of inflammation.
Read the detailed description
Glutamine, a nonessential amino acid, is preferred fuel for rapidly proliferating cells in human body. Those cells include the enterocytes in small intestine, lymphocytes, macrophages, and fibroblasts. Glutamine also transports nitrogen between tissues and serves as a precursor to glutathione which is a potent antioxidant. A healthy human body contains abundant glutamine, either from diet or from skeletal muscle tissue that synthesizes it.
During critical illness the demand for glutamine is increased. Rapid depletion of glutamine stores in critically ill patients has been described and correlated to increased mortality. Glutamine depletion may be deleterious in critical illness because of adverse effects on the essential functions mentioned above. For example glutamine depletion may cause gut mucosal barrier function to deteriorate, leading to bacterial translocation and enhanced systemic inflammatory response with increased risk for multisystem organ failure. Clinical trials performed in a wide range of patients with serious illness, including cancer, trauma, burn, major surgery and critical illness, have demonstrated possible benefits of glutamine supplementation. Interpretation of the results of multiple studies is made difficult based on differences in glutamine dosing, route of administration, population studied, and endpoints used.
Blood volume analysis has been shown to be a good measure of capillary leak. The DAXOR blood volume analyzer kit was recently approved by the FDA for blood volume analyses and also has the capacity of measuring capillary permeability by looking at the slope of albumin transudation. It is a simpler way to measure capillary permeability than other methods described.
Reviewing the previous study results, glutamine supplementation in parental form and with higher dose in various patient populations has shown evidence of being beneficial. Studies of enteral glutamine therapy have also showed benefits, but results are less consistent possibly because of the heterogeneous study methodology described above. Moreover, most of the studies are carried out in burn patients and surgical patients; there were few studies in critical ill medical patients. Finally no study has specifically looked at the mechanism via which glutamine has conferred protection.
Comparison: Critically ill patients given enteral tube feeds compared to critically ill patients given enteral tube feeds with supplemental glutamine.
- Conditions
- Critical Illness, Sepsis, Respiratory Insufficiency
- Being tested
- Glutamine
- Keywords
- Glutamine, Critical Illness, Enteral Feeding, Blood Volume Analysis
- Medical subject headings
- Critical Illness, Sepsis, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlutamineDrug
Group A patients will receive 0.5g/kg/day of enteral glutamine daily while they are receiving tube feeds or at the end of 28 days (whichever comes first)
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Will receive enteral glutamine Receives: Drug: Glutamine |
| B | No intervention | No enteral glutamine given |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Measured: 28 days
Length of ICU stay
Measured: 28 days
Number of Ventilator Days
Measured: 28 days
Number of days receiving antibiotics
Measured: 28 days
Secondary outcomes (6)
Change in APACHE Score
Measured: 72 hours
Change in Number of SIRS Criteria
Measured: 72 hours
Change in Capillary Leak as measured by blood volume analysis
Measured: 72 hours
Change in CRP
Measured: 72 hours
Correlation between capillary permeability and APACHE Score
Measured: 72 hours
Correlation between capillary permeability and Mortality
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2006 (estimated)
- Study startMay 2006
- Primary completionSep 2007
- Study completionSep 2007
Why it stopped: Unable to meet enrollment numbers
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (57)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christiana Care Health Services
- Sponsor type
- University, hospital or other
- Investigators
- Michael DePietro, M.D., Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00318331
- Sponsor's protocol ID
- Glutamine
- Status last verified
- Mar 2008
- First submitted
- 24 Apr 2006
- Last updated
- 13 Mar 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract. JPEN J Parenter Enteral Nutr. 1985 Sep-Oct;9(5):608-17. doi: 10.1177/0148607185009005608. No abstract available.
PubMed 3900455Gamrin L, Essen P, Forsberg AM, Hultman E, Wernerman J. A descriptive study of skeletal muscle metabolism in critically ill patients: free amino acids, energy-rich phosphates, protein, nucleic acids, fat, water, and electrolytes. Crit Care Med. 1996 Apr;24(4):575-83. doi: 10.1097/00003246-199604000-00005.
PubMed 8612406Conejero R, Bonet A, Grau T, Esteban A, Mesejo A, Montejo JC, Lopez J, Acosta JA. Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study. Nutrition. 2002 Sep;18(9):716-21. doi: 10.1016/s0899-9007(02)00847-x.
PubMed 12297203Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJ, Zandstra DF. Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med. 2001 Jan;27(1):84-90. doi: 10.1007/s001340000703.
PubMed 11280678Planas M, Schwartz S, Arbos MA, Farriol M. Plasma glutamine levels in septic patients. JPEN J Parenter Enteral Nutr. 1993 May-Jun;17(3):299-300. doi: 10.1177/0148607193017003299. No abstract available.
PubMed 8505843Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R, Morrow FD, Jacobs DO, Smith RJ, Antin JH, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann Intern Med. 1992 May 15;116(10):821-8. doi: 10.7326/0003-4819-116-10-821.
PubMed 1567096Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition. 1997 Apr;13(4):295-302.
PubMed 9178278Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M. Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med. 2001 Nov;29(11):2075-80. doi: 10.1097/00003246-200111000-00006.
PubMed 11700398Wischmeyer PE. Clinical applications of L-glutamine: past, present, and future. Nutr Clin Pract. 2003 Oct;18(5):377-85. doi: 10.1177/0115426503018005377.
PubMed 16215069Garrel D, Patenaude J, Nedelec B, Samson L, Dorais J, Champoux J, D'Elia M, Bernier J. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med. 2003 Oct;31(10):2444-9. doi: 10.1097/01.CCM.0000084848.63691.1E.
PubMed 14530749Oberhoffer M, Karzai W, Meier-Hellmann A, Bogel D, Fassbinder J, Reinhart K. Sensitivity and specificity of various markers of inflammation for the prediction of tumor necrosis factor-alpha and interleukin-6 in patients with sepsis. Crit Care Med. 1999 Sep;27(9):1814-8. doi: 10.1097/00003246-199909000-00018.
PubMed 10507603Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest. 2003 Jun;123(6):2043-9. doi: 10.1378/chest.123.6.2043.
PubMed 12796187Singleton KD, Serkova N, Beckey VE, Wischmeyer PE. Glutamine attenuates lung injury and improves survival after sepsis: role of enhanced heat shock protein expression. Crit Care Med. 2005 Jun;33(6):1206-13. doi: 10.1097/01.ccm.0000166357.10996.8a.
PubMed 15942332Wischmeyer PE. Can glutamine turn off the motor that drives systemic inflammation? Crit Care Med. 2005 May;33(5):1175-8. doi: 10.1097/01.ccm.0000162686.28604.81. No abstract available.
PubMed 15891373De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. 2005 May;33(5):1125-35. doi: 10.1097/01.ccm.0000162680.52397.97.
PubMed 15891348
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial Comparing Enteral Glutamine Supplementation to Standard of Care Enteral Feeding in Critical Illness
- ClinicalTrials.gov ID
- NCT00318331
- Acronym / sponsor ID
- Glutamine
- Conditions
- Critical Illness, Sepsis, Respiratory Insufficiency
- Keywords
- Glutamine, Critical Illness, Enteral Feeding, Blood Volume Analysis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to meet enrollment numbers
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Christiana Care Health ServicesUniversity, hospital or other
- Study start
- May 2006
- Primary completion
- Sep 2007 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 26 Apr 2006 (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.
Glutamine is an amino acid which is rapidly depleted in critical illness. It is used as energy by cells that line the gut, vital for immune system function, and works as an anti-oxidant. Glutamine supplementation has been shown to improve outcomes in ICU patients. We hypothesize that critically ill patients given extra glutamine will have less of an inflammatory response and therefore better outcomes than patients not given extra glutamine. Our study randomizes patients to tube feeding with OR without extra glutamine to see if it affects patient outcomes as well as markers of inflammation.
Detailed description
Glutamine, a nonessential amino acid, is preferred fuel for rapidly proliferating cells in human body. Those cells include the enterocytes in small intestine, lymphocytes, macrophages, and fibroblasts. Glutamine also transports nitrogen between tissues and serves as a precursor to glutathione which is a potent antioxidant. A healthy human body contains abundant glutamine, either from diet or from skeletal muscle tissue that synthesizes it.
During critical illness the demand for glutamine is increased. Rapid depletion of glutamine stores in critically ill patients has been described and correlated to increased mortality. Glutamine depletion may be deleterious in critical illness because of adverse effects on the essential functions mentioned above. For example glutamine depletion may cause gut mucosal barrier function to deteriorate, leading to bacterial translocation and enhanced systemic inflammatory response with increased risk for multisystem organ failure. Clinical trials performed in a wide range of patients with serious illness, including cancer, trauma, burn, major surgery and critical illness, have demonstrated possible benefits of glutamine supplementation. Interpretation of the results of multiple studies is made difficult based on differences in glutamine dosing, route of administration, population studied, and endpoints used.
Blood volume analysis has been shown to be a good measure of capillary leak. The DAXOR blood volume analyzer kit was recently approved by the FDA for blood volume analyses and also has the capacity of measuring capillary permeability by looking at the slope of albumin transudation. It is a simpler way to measure capillary permeability than other methods described.
Reviewing the previous study results, glutamine supplementation in parental form and with higher dose in various patient populations has shown evidence of being beneficial. Studies of enteral glutamine therapy have also showed benefits, but results are less consistent possibly because of the heterogeneous study methodology described above. Moreover, most of the studies are carried out in burn patients and surgical patients; there were few studies in critical ill medical patients. Finally no study has specifically looked at the mechanism via which glutamine has conferred protection.
Comparison: Critically ill patients given enteral tube feeds compared to critically ill patients given enteral tube feeds with supplemental glutamine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: GlutamineWill receive enteral glutamine |
| B | No intervention | –No enteral glutamine given |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Admission to MICU/ CICU
- Age greater than or equal to 18 years old
- Requirement for enteral nutrition
- Presence or planned insertion of central venous catheter as part of routine medical care
- Requirement for mechanical ventilation
Key exclusion criteria (6 listed)
- Female of child-bearing age (i.e. less than 45 years old)
- Enteral nutrition begun prior to randomization
- Receiving Total Parenteral Nutrition
- Requirement for protein restriction
- Creatinine >4 mg/dl
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 |
|---|---|---|
| GlutamineGroup A patients will receive 0.5g/kg/day of enteral glutamine daily while they are receiving tube feeds or at the end of 28 days (whichever comes first) | Drug | A |
Primary outcome
Mortality
Time frame: 28 days
Length of ICU stay
Time frame: 28 days
Number of Ventilator Days
Time frame: 28 days
Number of days receiving antibiotics
Time frame: 28 days
6 secondary outcomes
Change in APACHE Score
Time frame: 72 hours
Change in Number of SIRS Criteria
Time frame: 72 hours
Change in Capillary Leak as measured by blood volume analysis
Time frame: 72 hours
Change in CRP
Time frame: 72 hours
Correlation between capillary permeability and APACHE Score
Time frame: 72 hours
Correlation between capillary permeability and Mortality
Time frame: 72 hours
Results and safety
The study was stopped early (reason given: Unable to meet enrollment numbers). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2008.
- Background: PubMed 3900455Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract. JPEN J Parenter Enteral Nutr. 1985 Sep-Oct;9(5):608-17. doi: 10.1177/0148607185009005608. No abstract available.
- Background: PubMed 8612406Gamrin L, Essen P, Forsberg AM, Hultman E, Wernerman J. A descriptive study of skeletal muscle metabolism in critically ill patients: free amino acids, energy-rich phosphates, protein, nucleic acids, fat, water, and electrolytes. Crit Care Med. 1996 Apr;24(4):575-83. doi: 10.1097/00003246-199604000-00005.
- Background: PubMed 12297203Conejero R, Bonet A, Grau T, Esteban A, Mesejo A, Montejo JC, Lopez J, Acosta JA. Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study. Nutrition. 2002 Sep;18(9):716-21. doi: 10.1016/s0899-9007(02)00847-x.
- Background: PubMed 11280678Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJ, Zandstra DF. Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med. 2001 Jan;27(1):84-90. doi: 10.1007/s001340000703.
- Background: PubMed 8505843Planas M, Schwartz S, Arbos MA, Farriol M. Plasma glutamine levels in septic patients. JPEN J Parenter Enteral Nutr. 1993 May-Jun;17(3):299-300. doi: 10.1177/0148607193017003299. No abstract available.
- Background: PubMed 1567096Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R, Morrow FD, Jacobs DO, Smith RJ, Antin JH, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann Intern Med. 1992 May 15;116(10):821-8. doi: 10.7326/0003-4819-116-10-821.
- Background: PubMed 9178278Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition. 1997 Apr;13(4):295-302.
- Background: PubMed 11700398Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M. Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med. 2001 Nov;29(11):2075-80. doi: 10.1097/00003246-200111000-00006.
- Background: PubMed 16215069Wischmeyer PE. Clinical applications of L-glutamine: past, present, and future. Nutr Clin Pract. 2003 Oct;18(5):377-85. doi: 10.1177/0115426503018005377.
- Background: PubMed 14530749Garrel D, Patenaude J, Nedelec B, Samson L, Dorais J, Champoux J, D'Elia M, Bernier J. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med. 2003 Oct;31(10):2444-9. doi: 10.1097/01.CCM.0000084848.63691.1E.
- Background: PubMed 10507603Oberhoffer M, Karzai W, Meier-Hellmann A, Bogel D, Fassbinder J, Reinhart K. Sensitivity and specificity of various markers of inflammation for the prediction of tumor necrosis factor-alpha and interleukin-6 in patients with sepsis. Crit Care Med. 1999 Sep;27(9):1814-8. doi: 10.1097/00003246-199909000-00018.
- Background: PubMed 12796187Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest. 2003 Jun;123(6):2043-9. doi: 10.1378/chest.123.6.2043.
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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.
Michael DePietro, M.D. principal investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Glutamine in people with Critical Illness and Sepsis, run by Christiana Care Health Services 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 6 inclusion and 6 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: stopped early, as of the sponsor's last update on 13 Mar 2008. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Unable to meet enrollment numbers). Results are not available in the source record.
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?
Mortality (time frame: 28 days). The study lists 4 primary outcomes in all. 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 NCT00318331, which also lists 57 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 Mar 2008.