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

Study Overview
=================
Brief Summary
-----------------
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.

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

Official Title
-----------------
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

Conditions
-----------------
Malnourishment, Gastrointestinal Tumors

Intervention / Treatment
-----------------
* Dietary Supplement: Glutamine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glutamin<br> | Dietary Supplement: Glutamine<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 30g oral maltodextrin / day for 5 days before surgery<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Malnourishment, Gastrointestinal tumors, Immunocompetence