Effect of Gutamine Administration in the Innate Immune System Response in ICU Patients.

Sponsor

Hospital Universitari Son Dureta (Other)

Overall Status

Completed

CT.gov ID

NCT01250080

Collaborator

Espen (Other), This research prize was funded by Nestle Nutrition Institute and by Fresenius Kabi. (Other)

Enrollment

Location

Arms

Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Glutamine is the most abundant nonessential amino acid in the human body. Besides its role as a constituent of proteins and its importance in amino acid transamination, glutamine may modulate immune cells.

The innate immune system is the first line of host defence against pathogens and in most cases sufficient to eliminate invading microbes. Mammalian Toll-like receptors (TLR) comprise a family of germ line-encoded trans-membrane receptors which activation leads to the induction of inflammatory responses, phagocytosis but also to the development of antigen specific adapative immunity.

It has been postulated though not formally proven yet that glutamine beneficial effect could be due to a positive effect on the innate immune system. Given the importance of TLRs and TLRs-dependent signalling in host defence against infections we hypothesized that glutamine may increase the expression and/or functionality of TLRs which in turn may have beneficial effects to clear infections.

Condition or Disease	Intervention/Treatment	Phase
Moderate to Severe Trauma, as Defined by an Injury Severity Score (ISS) > 12 Points Were Included in the Study.	Dietary Supplement: Total Parenteral Nutrition with Glutamine Other: Total Parenteral Nutrition without glutamine	N/A

Detailed Description

Objective: To evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the

ICU. Specifically the next variables were measured:

Expression of TLR2 and TLR4 in peripheral blood monocytes was determined by flow cytometry
To study the functionality of TLR2 and TLR4, monocytes were stimulated with TLR specific agonists and cytokines were measured in cell culture supernatants. We determined the concentration of IL-1β, IL-6, TNFα and IL-10 in cell culture supernatants using a bead array ELISA.
To determine the phagocytic capability of monocytes, live Escherichia coli expressing green fluorescent protein was added to 100 μL of whole blood collected in K2-anticoagulation medium tubes. Bacteria were added at a ratio of 100 bacteria per monocyte. The analyses were carried out in an Epics XL flow cytometer.

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

Randomized

Masking:

Single (Outcomes Assessor)

Study Start Date :

Jan 1, 2007

Actual Primary Completion Date :

Jun 1, 2008

Actual Study Completion Date :

Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glutamine	Dietary Supplement: Total Parenteral Nutrition with Glutamine daily glutamine supplement of 0.35 g/kg weight as N2-L-Alanyl-L-Glutamine (0.5 g/kg/d - Dipeptiven Fresenius Kabi España) during five days.
Sham Comparator: Control	Other: Total Parenteral Nutrition without glutamine The control group received a supplemental volume of the basic TPN solution to achieve an isocaloric an isonitrogenated formula with the study group.

Arm

Intervention/Treatment

Experimental: Glutamine

Dietary Supplement: Total Parenteral Nutrition with Glutamine

daily glutamine supplement of 0.35 g/kg weight as N2-L-Alanyl-L-Glutamine (0.5 g/kg/d - Dipeptiven Fresenius Kabi España) during five days.

Sham Comparator: Control

Other: Total Parenteral Nutrition without glutamine

The control group received a supplemental volume of the basic TPN solution to achieve an isocaloric an isonitrogenated formula with the study group.

Outcome Measures

Primary Outcome Measures

-Expression of TLR2 and TLR4 in peripheral blood monocytes was determined by flow cytometry []

Secondary Outcome Measures

-To study the functionality of TLR2 and TLR4, monocytes were stimulated with TLR specific agonists and cytokines were measured in cell culture supernatants. []
- To determine the phagocytic capability of monocytes, live Escherichia coli expressing green fluorescent protein was added to 100 μL of whole blood collected in K2-anticoagulation medium tubes. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 18 and 75 years (inclusive).
Moderate to severe trauma, as defined by an Injury Severity Score (ISS) > 12 points were included in the study
Traumatic patients who required total parenteral nutrition

Exclusion Criteria:

Patients who were under 17 and over 76 years of age,
Patients whose life expectancy was less than 5 days
Patientes allergic to glutamine.
Patients with any basic pathology included any serious immune system condition (diabetes, HIV, lupus, etc.) or who, in their long-term treatment prior to admission to ICU, received corticoids or any other immunosuppressant medication.
Pregnant women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Intensive Care Unit. Hospital Universitario Son Dureta	Palma Mallorca	Illes Balears	Spain	07014

Sponsors and Collaborators

Hospital Universitari Son Dureta
Espen
This research prize was funded by Nestle Nutrition Institute and by Fresenius Kabi.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT01250080

Other Study ID Numbers:

IB709/06

First Posted:

Nov 30, 2010

Last Update Posted:

Nov 30, 2010

Last Verified:

Sep 1, 2008

Study Results

No Results Posted as of Nov 30, 2010