The Impact of Preoperative Oral Glutamine Intake on the Immunocompetence and Outcomes of Malnourished Patients Undergoing Major Abdominal Surgery Due to Malignancies (Glutaminprojec)

The Impact of Preoperative Oral Glutamine Intake on the Immunocompetence and Outcomes of Malnourished Patients Undergoing Major Abdominal Surgery Due to Malignancies - A Randomized, Placebo-controlled Pilot Study

Malnutrition occurs in up to 50% of patients requiring elective surgery for neoplastic diseases. It exerts a detrimental influence on outcome of surgery, because it can suppress immune function, exaggerate stress response and cause organ system dysfunction. Increased susceptibility to infection, protracted wound healing, impaired blood clotting and vessel wall fragility have been shown to be the leading causes of postoperative morbidity and mortality in malnourished patients undergoing major surgical resections.

This trial is designed as a prospective randomized, double-blinded, placebo-controlled pilot study in a academic single center in Switzerland. A total of 50 malnourished patients with gastro-intestinal tumors will receive orally glutamine or placebo-treatment during a period of 5 days prior to surgery. The investigators hypothesize that oral Glutamine administration is feasible, well tolerated, will decrease postoperative morbidity, will suppress postoperative cell damage and inflammatory response, and will improve the perioperative immunocompetence of the patients.

Study Overview

• Status: Completed
• Conditions: Malnourishment; Gastrointestinal Tumors
• Intervention / Treatment: Dietary supplement: Glutamine; Drug: Placebo

Detailed Description

Background

Malnutrition occurs in up to 50% of patients requiring elective surgery for neoplastic diseases. It exerts a detrimental influence on outcome of surgery, because it can suppress immune function, exaggerate stress response and cause organ system dysfunction. Increased susceptibility to infection, protracted wound healing, impaired blood clotting and vessel wall fragility have been shown to be the leading causes of postoperative morbidity and mortality in malnourished patients undergoing major surgical resections.

Immuno- or pharmaconutrition, defined as enteral or parenteral nutritional therapy based on a variety of products, such as omega-3-fatty acids, glutamine, arginine, sulfur-containing amino acids, nucleotides and anti-oxidants, is thought to have beneficial effects on postoperative recovery in a wide variety of surgical patients. Studies have shown its clinical effectiveness in terms of reduced postoperative complications, shortening the hospital stay and reduced hospitalization costs. Torosian et al. showed that severely malnourished patients benefit from preoperative nutrition, which reduce postoperative complications by 20%.

Although there is clinical evidence for the administration of immunonutrition to patients in the perioperative period, our understanding of the optimal type and time of immunonutrition, the characteristics of patients that benefit most, as well as the immunological mechanisms responsible for its beneficial effect is limited.

Objective

To assess in malnourished cancer patients the effect of 30g oral glutamine/day (3 sachets KABI® glutamine, Fresenius Kabi/day) for a preoperative course of 5 days on:

1. Postoperative morbidity (surgical site infections, pneumonia, sepsis, incidence of wound and fascial dehiscence, incisional hernia, anastomotic break down)
2. Nutritional status of the patients
3. Postoperative cell damage and inflammatory response
4. Perioperative immunocompetence

Methods

Seven days before surgery, the patients will receive a tetanus booster shot and will be randomly enrolled in either the 'glutamine group' or into the 'placebo group'. The patients as well as the responsible surgeons will be blinded.

• Patients in the 'glutamine group' will receive 30g oral glutamine / day for 5 days before surgery.
• Patients in the 'control group' will receive 30g oral maltodextrin / day for 5 days before surgery.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Berne, Switzerland, 3010
    • Department of visceral surgery and transplant surgery, Berne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed and surgically resectable carcinomas
• Candidates for elective surgery with an estimated surgical stress score
• A Nutritional Risk Screening 2002 (NRS-200232) score ≥3
• Age ≥ 18 years
• Completed primary immunization with tetanus toxoid
• Last tetanus booster ≥10 years back
• Informed consent

Exclusion Criteria

• Refusal to participate
• Clinically relevant alterations of the pulmonary renal of hepatic function
• Insulin-dependent diabetes mellitus
• Pre-existing autoimmune diseases and immune-deficiencies
• Neutropenia
• Pregnancy
• Age <18 years
• Last tetanus booster <10 years back
• Ongoing infection
• Intestinal obstruction at the time of entry into the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 30g oral maltodextrin / day for 5 days before surgery
Active Comparator: Glutamin	Dietary supplement: Glutamine; 30g oral glutamine / day for 5 days before surgery. Glutamine is an important nonessential amino acid and its intracellular concentration is much higher than that of other amino acids. Glutamine is released in large quantities from skeletal muscle and serves as an important carrier and donor of nitrogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Morbidity	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Postoperative cell damage	Up to seven days after surgery
Inflammatory response	Up to seven days after surgery
Nutritional status	Up to seven days after surgery
Perioperative immunocompetence	Seven and one day(s) before surgery. Postoperative week 1 and 6.

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Fresenius Kabi
• Investigators: Principal Investigator: Beat Schnüriger, PD Dr. med., Department of visceral surgery and transplant surgery, Berne University Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): February 10, 2018
• Study Completion (Actual): February 12, 2018

Study Registration Dates

• First Submitted: March 5, 2012
• First Submitted That Met QC Criteria: March 12, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Actual): February 13, 2018
• Last Update Submitted That Met QC Criteria: February 12, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Malnourishment; Gastrointestinal tumors; Immunocompetence
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Nutrition Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Malnutrition
• Other Study ID Numbers: 170/11

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No