Dipeptide Alanyl Glutamine and Postoperative Insulin Resistance in Colon Carcinoma Patients (AIRCo)

Rationale: It is well known that insulin resistance occurs after mediocre and intensive surgery, such as colon cancer surgery. Disturbances in insulin action negatively affect the postoperative recovery, either by prolonging the capacity of the body to regain normal function, or by increasing the metabolic stress and the risk for complications. Several studies have shown that focusing therapies on improving insulin resistance is successful. Experimental studies have shown that antioxidant agents, like glutamine (a precursor of glutathione), improve insulin sensitivity. The hypothesis of this study is that perioperative parenteral or enteral administration of glutamine, given as the dipeptide alanyl-glutamine, will reduce or prevent postoperative insulin resistance in colon cancer patients. The study will also be focused on the different routes of administration, because of the expected differential metabolic effects.

Objective: The investigators' primary objective is to study whether intravenous or enteral administration of the dipeptide alanyl-glutamine will reduce or prevent postoperative insulin resistance in colon cancer patients.

Study design: A double-blinded, placebo controlled randomised, pilot study at the Surgery Department of the Medical Center Alkmaar.

Study population: Thirty patients of male gender and any ethnicity, who will undergo elective open abdominal colon surgery for colon cancer, aged 18-75 years.

Intervention: Patients will receive dipeptide alanyl-glutamine intravenously or enterally, starting 24 hours prior to surgery, until 24 hours after surgery in the dosage of 0.5 g/kg/day, or saline (control group), for the same period of time.

Main study parameters/endpoints: The main study parameter is postoperative insulin resistance. Secondary study parameters are lipolysis, oxidative stress and glucoregulatory hormones. Muscle, liver and fat biopsies will be taken to study insulin sensitive as well as inflammatory pathways.

Study Overview

• Status: Unknown
• Conditions: Colon Carcinoma
• Intervention / Treatment: Drug: Dipeptide Alanyl-Glutamine; Drug: Dipeptide Alanyl-Glutamine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hamit Cakir, MD; Phone Number: 0031725484444; Email: h.cakir@mca.nl

Study Locations

• Netherlands
  • Noord holland
    • Alkmaar, Noord holland, Netherlands, 1815 JD
      • Recruiting
      • Medical Center Alkmaar
      • Contact: Hamit Cakir, MD; Phone Number: 0031725484444; Email: h.cakir@mca.nl
      • Principal Investigator: Alexander PJ Houdijk, MD, PhD
      • Sub-Investigator: Hamit Cakir, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age between 18 and 75 years
• Colon cancer patients scheduled for elective open abdominal surgery
• Capable of giving informed consent

Exclusion Criteria:

• Patients who are participating in another clinical trial
• Unable to receive oral intake
• Major malabsorption disorder of the gut
• Patients with diabetes mellitus
• BMI above 30 kg/m2
• Use of certain medication: thyroid medication, corticosteroids, diuretic medication
• Known bleeding disorders or increased PTT and or APTT
• Any medical condition except for colon cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dipeptiven Arm Enteral	Drug: Dipeptide Alanyl-Glutamine; Intravenous supplementation of the dipeptide alanyl-glutamine is started 24 hours prior to surgery (dosage glutamine: 0,5 g/kg/day, and continued 24 hours postoperatively.; Drug: Dipeptide Alanyl-Glutamine; Enteral supplementation of the dipeptide alanyl-glutamine is started 24 hours prior to surgery (dosage glutamine: 0,5 g/kg/day, and continued 24 hours postoperatively.
Placebo Comparator: Placebo Arm Enteral and Intravenously	Drug: Placebo; Intravenous and enteral supplementation of placebo is started 24 hours prior to surgery and continued 24 hours postoperatively.
Active Comparator: Dipeptiven ARM Intravenously	Drug: Dipeptide Alanyl-Glutamine; Intravenous supplementation of the dipeptide alanyl-glutamine is started 24 hours prior to surgery (dosage glutamine: 0,5 g/kg/day, and continued 24 hours postoperatively.; Drug: Dipeptide Alanyl-Glutamine; Enteral supplementation of the dipeptide alanyl-glutamine is started 24 hours prior to surgery (dosage glutamine: 0,5 g/kg/day, and continued 24 hours postoperatively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The effect of intravenously and enterally administered dipeptide alanyl-glutamine preoperatively on postoperative insulin resistance in colon cancer patients.given, on postoperative insulin resistance in colon cancer patients.	Before and 1 day after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
The effect of the dipeptide alanyl-glutamine on components of the insulin signalling cascade in muscle tissue.	Before and 1 day after surgery
The effect of the dipeptide alanyl-glutamine on the systemic inflammatory response as well as on inflammatory pathways in muscle.	Before and 1 day after surgery
The effect of the dipeptide alanyl-glutamine on the amino acid concentration in muscle tissue.	Before and 1 day after surgery
The effect of the dipeptide alanyl-glutamine on antioxidant/oxidant parameters in the circulating compartment.	Before and 1 day after surgery
The effect of dipeptide alanyl-glutamine on the inflammatory response in the liver	During surgery
The effect of dipeptide alanyl-glutamine on lipolysis.	Before and 1 day after surgery
The effect of dipeptide alanyl-glutamine on key enzymes involved in glucose production.	Before and 1 day after surgery

Collaborators and Investigators

• Sponsor: Medical Center Alkmaar
• Investigators: Study Director: Alexander PJ Houdijk, MD,PhD, MCA Alkmaar

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): May 1, 2013

Study Registration Dates

• First Submitted: June 16, 2009
• First Submitted That Met QC Criteria: June 16, 2009
• First Posted (Estimate): June 17, 2009

Study Record Updates

• Last Update Posted (Estimate): July 21, 2011
• Last Update Submitted That Met QC Criteria: July 20, 2011
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Insulin sensitivity; Lipolysis; Dipeptide Alanyl-Glutamine; Intracellular signaling; Antioxidant/oxidant parameters; Inflammatory response in the liver
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Hyperinsulinism; Colorectal Neoplasms; Carcinoma; Insulin Resistance; Colonic Neoplasms
• Other Study ID Numbers: AIRCo05.02.2009/2