Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to find out whether adding insulin after current colorectal cancer surgery promotes making and keeping proteins in the body, and to find out whether or not this effect can be further increased by increasing the amount of protein given.

Official Title
-----------------
Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Dietary Supplement: Travasol (amino acid injection)
* Drug: Insulin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: American Society of Anesthesiologists class<3 age>18 years colorectal surgery for non-metastatic colorectal adenocarcinoma including right and left hemicolectomy, transverse, subtotal and total colectomy sigmoid and low anterior resection ability to give informed consent Exclusion Criteria: BMI>30 Kg/meter squared confirmed diagnosis of diabetes mellitus or a HbA1c>6.0% significant cardiorespiratory, hepatic, renal and neurological disease musculoskeletal or neuromuscular disease ingestion of drugs known to affect protein, glucose and lipid metabolism (e.g. steroids) severe anemia (hemoglobin<10 g/dL pregnancy history of severe sciatica, back surgery or other conditions which contraindicate the use of epidural catheters

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin, Travasol (35%) postop<br>Insulin (hyperinsulinemic-normoglycemic clamp) with Travasol (amino acid supplementation) given from start of surgery to 6 hours after, at an amount of 35% of patient's energy expenditure as measured before surgery, . | Dietary Supplement: Travasol (amino acid injection)<br>* an amino acid supplementation infused intravenously containing essential and non-essential amino acids<br>* Other names: Travasol;Drug: Insulin<br>* After the insertion of an arterial catheter and obtaining a baseline arterial blood glucose value, 2 units of insluin will be administered iv followed by an infusion of 2 microunits/kg*min. Ten minuts after starting the insulin, and when the the blood glucose is<6 mmol/L, dextrose 20% supplemented with phosphate (30mmol/L) will be infused. Blood glucose levels measured every 15 minutes and the dextrose infusion rate adjusted to maintain arterial glycemia between 4 and 6 mmol/L until end of study.<br>* Other names: Hyperinsulinemic-normoglycemic clamp;|
| Experimental: Insulin, Travasol (20%) postop<br>Insulin (hyperinsulinemic-normoglycemic clamp) with Travasol (amino acid infusion), given from start of surgery to 6 hours after, at an amount of 20% of patient's energy expenditure as measured before surgery. | Dietary Supplement: Travasol (amino acid injection)<br>* an amino acid supplementation infused intravenously containing essential and non-essential amino acids<br>* Other names: Travasol;Drug: Insulin<br>* After the insertion of an arterial catheter and obtaining a baseline arterial blood glucose value, 2 units of insluin will be administered iv followed by an infusion of 2 microunits/kg*min. Ten minuts after starting the insulin, and when the the blood glucose is<6 mmol/L, dextrose 20% supplemented with phosphate (30mmol/L) will be infused. Blood glucose levels measured every 15 minutes and the dextrose infusion rate adjusted to maintain arterial glycemia between 4 and 6 mmol/L until end of study.<br>* Other names: Hyperinsulinemic-normoglycemic clamp;|
| Placebo Comparator: Insulin, no protein after surgery<br>Insulin (hyperinsulinemic-normoglycemic clamp, an insulin infusion between 2 and 5 microunits/kg with glucose at a variable rated titrated to maintain normoglycemia, blood glucose 4-6 mmol/L) with no protein supplementation from start of surgery to 6 hours after. | Drug: Insulin<br>* After the insertion of an arterial catheter and obtaining a baseline arterial blood glucose value, 2 units of insluin will be administered iv followed by an infusion of 2 microunits/kg*min. Ten minuts after starting the insulin, and when the the blood glucose is<6 mmol/L, dextrose 20% supplemented with phosphate (30mmol/L) will be infused. Blood glucose levels measured every 15 minutes and the dextrose infusion rate adjusted to maintain arterial glycemia between 4 and 6 mmol/L until end of study.<br>* Other names: Hyperinsulinemic-normoglycemic clamp;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net protein balance | The difference in total body protein after randomization to one of the three treatment arms. | 6 hours after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colorectal cancer, protein recovery, perioperative nutrition, hyperinsulinemia, normoglycemia, hyperinsulinemic-normoglycemic clamp, anabolism