Modulation of Systemic Inflammatory Response in Critically Ill Children After Glutamine Supplementation

September 5, 2013 updated by: Hospital Sant Joan de Deu

This study aims to describe the use of glutamine supplementation in the modulation of inflammatory response in critically ill pediatric patients and to determine if this decrease leads to clinical improvement in morbidity and mortality in these patients. Thus, these patients' diet could be supplemented with glutamine in order to improve their evolution.

Hypothesis:

From the data obtained in the study of the literature the investigators consider that:

Critically ill patients have a deficit of glutamine either because of an increase in its consumption or a decrease in its availability, and therefore blood glutamine levels are low.

Critically ill patients have elevated blood levels of pro-inflammatory substances (IL-6).

In these patients tissue lesion inhibitors (HSP-70) in the blood are decreased. The administration of glutamine supplements to these patients decreases oxidative stress due to the increase in HSP-70.

Inflammation inhibitory substances (IL-10) in the blood are decreased in these patients.

The administration of glutamine supplements in these patients increase IL-10 levels.

Glutamine supplements decrease the inflammatory response with a decrease in IL-6 levels.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Objective

This study aims to describe the use of glutamine supplementation in the modulation of inflammatory response in critically ill pediatric patients and to determine if this decrease leads to clinical improvement in morbidity and mortality in these patients. Thus, these patients' diet could be supplemented with glutamine in order to improve their evolution.

In recent years numerous studies have been conducted and published on the different factors, amongst them glutamine, that could modulate the inflammatory response of critically ill patients thus reducing the impact this response has and its progression to multi-organ failure.

Glutamine (Gln) is the most abundant amino acid in the body and is mainly synthesised in skeletal muscle. It is a non-essential amino acid that is produced is sufficient quantities in good states of health. Plasma levels are above 0.6 mmol/L, and 50% is found in the free form in plasma1. This amino acid not only acts as a source of energy but it is also involved in the synthesis of other amino acids, nucleotides, nucleic acids, sugars, amines, proteins and different biologically active molecules2. Other functions are: maintenance of the internal acid-base homeostasis, urea synthesis, glyconeogenesis, neurotransmission, and cell differentiation and proliferation. It is also the main energy substrate for the rapidly proliferating cells (enterocytes) and of multiple immune cells (macrophages, monocytes, lymphocytes). It also takes part in the protection of cells and tissues inducing expression of the heat shock proteins3.

In recent years, numerous studies have been performed to determine the effect of Gln, both by enteral and parenteral route, on the evolution of critically ill patients. These studies were conducted in animals and in humans, mainly adults. However, there is little reference in the literature to studies in children. The studies are based on the use of glutamine as a dietary supplement mainly in patients with neoplastic disease or inflammatory bowel disease. It has also been studied as a supplement in premature infants, but there are very few studies in critically ill children.

In the last year many studies have been published on the use of glutamine. The effect of glutamine supplementation on the intestinal mucosal barrier in rabbits under haemorrhagic shock was studied. Shock was induced by blood withdrawing from the femoral artery; the rabbits were randomised to three groups (control, low dose glutamine and high dose glutamine). Plasma levels of diamine oxidase and IL-8 were measured and a histological examination of the terminal ileum was performed. The results demonstrated a lower inflammatory and oxidative response in the rabbits who had received Gln supplementation37. Another study in rats measured the effect of the dipeptide Arginin - Gln on endothelial cell growth factor levels in retinal pigment epithelial cell cultures and on the inhibition of neovascularisation in oxygen-induced retinopathy. The authors concluded that they decreased with the administration of this dipeptide38. Another factor studied in critically ill patients was the oxidative activity measured as diamine oxidase activity and D-lactate content39. Protection against infection and decrease in insulin resistance in critically ill patients is still being studied 21,22, 32, 40, 41. Contradictory findings have been reported therefore new studies are required in systematic reviews.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • Esplugues de Llobregat, Barcelona, Spain, 08950
        • Hospital Sant Joan de Déu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 14 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

1. Patients aged between 1 month and 14 years who require parenteral nutrition according to the criteria of our unit and who comply with the following diagnoses:

  • Local or systemic infection
  • Post abdominal surgery
  • Polytraumatised

Parenteral nutrition indications:

  • Intestinal resections
  • Bowel obstruction or post-surgery
  • Risk of intestinal ischaemia due to hypotension of hypoxaemia

Exclusion Criteria:

  1. Legal representative does not give consent.
  2. Patients with previous underlying diseases (renal impairment, hepatic impairment, inflammatory bowel disease, rheumatic diseases, metabolic diseases, immunocompromised).
  3. Mild liver impairment on admittance (hepatitis, colostasis).
  4. Post cardiac surgery with extracorporeal circulation.
  5. Patients referred from other hospitals with a clinical evolution of over 48 hours.
  6. Patients aged less than one month and over 14 years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: solution of amino acids with glutamine
Group 1 as the experimental group who will be administered a solution of amino acids supplemented with glutamine
Dietary supplement: solution of amino acids supplemented with glutamine
parenteral nutrition by range of ages (recommendation from ESPGHAN and ESPEN:1 month to 3 years, 3 to 5 years, 6 to 12 and standard adult).Study Parenteral nutrition will be assessed the first 5 days.
Other Names:
  • (Aminoven Infant® or Vamin®) with glutamine (Dipeptiven®)
OTHER: amino acids solution without glutamine
Group 2:control group will be administered a solution of amino acids (Aminoven Infant® or Vamin®) not supplemented with glutamine
Dietary supplement: amino acids not supplemented with glutamine
parenteral nutrition by range of ages (recommendation from ESPGHAN and ESPEN:1 month to 3 years, 3 to 5 years, 6 to 12 and standard adult).Study Parenteral nutrition will be assessed the first 5 days.
Other Names:
  • (Aminoven Infant® or Vamin®) with glutamine (Dipeptiven®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary study endpoint is to determine if there are any differences in inflammatory response in patients supplemented with glutamine compared to those who receive a standard diet without a glutamine supplement.
Time Frame: baseline-day2-day5
Laboratory measures: IL-6, IL-10, HSP-70
baseline-day2-day5

Secondary Outcome Measures

Outcome Measure
Time Frame
As secondary endpoints the clinical response of the two groups of patients was assessed with respect to the occurrence of infections, multi-organ failure, mean stay in the unit and mortality.
Time Frame: During 27 days
During 27 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Sant Joan de Deu

Collaborators

Fundació Sant Joan de Déu
Spanish National Health System

Investigators

  • Principal Investigator: Iolanda Jordan, PhMD, Hospital Sant Joan de Déu

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (ACTUAL)

July 1, 2012

Study Completion (ACTUAL)

May 1, 2013

Study Registration Dates

First Submitted

June 3, 2011

First Submitted That Met QC Criteria

June 6, 2011

First Posted (ESTIMATE)

June 7, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

September 6, 2013

Last Update Submitted That Met QC Criteria

September 5, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCIHSJD5

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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