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

Sponsor

Medical Center Alkmaar (Other)

Overall Status

Unknown status

CT.gov ID

NCT00922688

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colon Carcinoma	Drug: Dipeptide Alanyl-Glutamine Drug: Placebo Drug: Dipeptide Alanyl-Glutamine	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

Dipeptide Alanyl Glutamine and Postoperative Insulin Resistance in Colon Carcinoma Patients

Study Start Date :

Dec 1, 2010

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dipeptiven Arm Enteral	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.

Arm

Intervention/Treatment

Active Comparator: Dipeptiven Arm Enteral

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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