Trial of Enteral Glutamine on Clinical Outcomes in Critically Ill Patients

Effects of Enteral Glutamine on Inflammatory Response, Immune System Function and Clinical Outcomes in Hospitalized Patients With Enteral Feeding in Intensive Care Unit

Glutamine supplementation has beneficial effects on morbidity and mortality in critically ill patients, possibly in part through an attenuation of the proinflammatory cytokine response and a Immune function. In this trial intensive care unit patients with enteral feeding will receive either enteral glutamine or maltodextrin as placebo for 28 days.

Study Overview

• Status: Completed
• Conditions: Inflammation; Critical Illness; Enteral Nutrition; Multiple Organ Failure; Infection Complication
• Intervention / Treatment: Drug: Glutamin; Other: Maltodextrin

Detailed Description

A randomized, double blind, controlled trial will be conducted in general intensive care unit (ICU) in Tehran, Iran. After a full review of the inclusion and exclusion criteria and explanation of the risks and benefits of the study, written consent form will be completed. The participants are 200 eligible hospitalized patients with enteral feeding in ICU, aged ≥ 18 years. Intervention patients will be received 0.3 g/kg/day of glutamine along with enteral formula for 28 days and control patients will be received maltodextrin along with enteral formula for 28 days. Patients will be evaluated for occurrence of new infection, organ failure, duration of stay in ICU, 28 days and 6 months mortality and inflammatory and immune markers.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences
  • Tehran, Iran, Islamic Republic of
    • Shohada Tajrish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (>18 years old) admitted to ICU
• Start of study intervention within 48 hours after ICU admission
• Expected to require enteral nutrition for at least 72 hours aiming for full enteral nutrition and receive at least 80 percent of enteral formula during the first 48 hour
• Written informed consent of patient or written informed consent of legal representative

Exclusion Criteria:

• Enrollment in a related ICU interventional study
• Requiring other specific enteral nutrition for medical reason
• Death or Discharge before 5th day
• Having any contra-indication to receive enteral nutrition
• Pregnant patients or lactating with the intent to breastfeed
• Requiring other specific enteral nutrition for medical reason
• BMI <18 or > 40.0 kg/m2
• Have life expectancy of <6 mo
• Patients who are moribond
• Liver cirrhosis- Child's class C liver disease
• Have seizure disorder requiring anticonvulsant
• History of allergy or intolerance to the study product components
• Receiving glutamine during two weeks before start study product
• Have other reasons

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Glutamin; Intervention patients will be received enteral formula and glutamine 0.3 g/kg/day given via nasogastric tube as boluses q 4hrs.	Drug: Glutamin; Enteral Glutamine 0.3g/kg/day powdered glutamine to be mixed in with water and given via nasogastric tube q4 hrs; Other Names: L-glutamine
PLACEBO_COMPARATOR: maltodextrin; Control patients will be received enteral formula and maltodextrin mixed in with water and given via nasogastric tube as boluses q 4hrs.	Other: Maltodextrin; Maltodextrin mixed with water given via NG tube Q 4 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of infection	Incidence of infections	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Inflammatory Markers	Inflammatory factors	baseline, Day 5, Day 10
Serum Immunity Markers		baseline, Day 5, Day 10
Length of stay in ICU		Day 28
28-day Mortality	Day 28	Day 28
6-month mortality	month 6	month 6

Other Outcome Measures

Outcome Measure	Time Frame
Serum Glutamin	baseline, Day 5, Day 10

Collaborators and Investigators

• Sponsor: Shahid Beheshti University
• Investigators: Study Chair: Zahra Vahdat Shariatpanahi, MD, PhD, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Publications and helpful links

General Publications

• Hall JC, Dobb G, Hall J, de Sousa R, Brennan L, McCauley R. A prospective randomized trial of enteral glutamine in critical illness. Intensive Care Med. 2003 Oct;29(10):1710-6. doi: 10.1007/s00134-003-1937-2. Epub 2003 Aug 16.
• McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, McCarthy MS, Davanos E, Rice TW, Cresci GA, Gervasio JM, Sacks GS, Roberts PR, Compher C; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016 Feb;40(2):159-211. doi: 10.1177/0148607115621863. No abstract available. Erratum In: JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1200.
• Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013 Apr 18;368(16):1489-97. doi: 10.1056/NEJMoa1212722. Erratum In: N Engl J Med. 2013 May 9;368(19):1853. Dosage error in article text.
• van Zanten AR, Sztark F, Kaisers UX, Zielmann S, Felbinger TW, Sablotzki AR, De Waele JJ, Timsit JF, Honing ML, Keh D, Vincent JL, Zazzo JF, Fijn HB, Petit L, Preiser JC, van Horssen PJ, Hofman Z. High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial. JAMA. 2014 Aug 6;312(5):514-24. doi: 10.1001/jama.2014.7698.
• Kreymann KG, Berger MM, Deutz NE, Hiesmayr M, Jolliet P, Kazandjiev G, Nitenberg G, van den Berghe G, Wernerman J; DGEM (German Society for Nutritional Medicine); Ebner C, Hartl W, Heymann C, Spies C; ESPEN (European Society for Parenteral and Enteral Nutrition). ESPEN Guidelines on Enteral Nutrition: Intensive care. Clin Nutr. 2006 Apr;25(2):210-23. doi: 10.1016/j.clnu.2006.01.021. Epub 2006 May 11.
• McQuiggan M, Kozar R, Sailors RM, Ahn C, McKinley B, Moore F. Enteral glutamine during active shock resuscitation is safe and enhances tolerance of enteral feeding. JPEN J Parenter Enteral Nutr. 2008 Jan-Feb;32(1):28-35. doi: 10.1177/014860710803200128.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 10, 2016
• Primary Completion (ACTUAL): August 25, 2018
• Study Completion (ACTUAL): September 10, 2018

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (ESTIMATE): December 21, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 13, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Intensive Care Unit; Enteral Nutrition; Immune System; inflammatory; Critical Care Outcomes; Glutamin
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Shock; Inflammation; Critical Illness; Multiple Organ Failure
• Other Study ID Numbers: 1395/670

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No