Enteral Glutamine in Critical Illness

Sepsis Clinical Trial

Official title:

Randomized Clinical Trial Comparing Enteral Glutamine Supplementation to Standard of Care Enteral Feeding in Critical Illness

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00318331
• Other study ID #: Glutamine
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: April 24, 2006
• Last updated: March 10, 2008
• Start date: May 2006
• Est. completion date: September 2007

Study information

• Verified date: March 2008
• Source: Christiana Care Health Services
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Illness
• Pulmonary Valve Insufficiency
• Respiratory Insufficiency
• Sepsis

Intervention

Drug:
• Glutamine
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)

Locations

Country	Name	City	State
United States	Christiana Hospital	Newark	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Christiana Care Health Services

Country where clinical trial is conducted

United States, 

References & Publications (57)

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* Note: There are 57 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality		28 days	Yes
Primary	Length of ICU stay		28 days	No
Primary	Number of Ventilator Days		28 days	No
Primary	Number of days receiving antibiotics		28 days	No
Secondary	Change in APACHE Score		72 hours	No
Secondary	Change in Number of SIRS Criteria		72 hours	No
Secondary	Change in Capillary Leak as measured by blood volume analysis		72 hours	No
Secondary	Change in CRP		72 hours	No
Secondary	Correlation between capillary permeability and APACHE Score		72 hours	No
Secondary	Correlation between capillary permeability and Mortality		72 hours	No