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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Dietary supplement: Travasol (amino acid injection); Drug: Insulin

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H8A1A1
      • McGill University Health Centre (MUHC) - Royal Victoria Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin, Travasol (35%) postop; 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); an amino acid supplementation infused intravenously containing essential and non-essential amino acids; Other Names: Travasol; Drug: Insulin; 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.; Other Names: HNC; Hyperinsulinemic-normoglycemic clamp
Experimental: Insulin, Travasol (20%) postop; 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); an amino acid supplementation infused intravenously containing essential and non-essential amino acids; Other Names: Travasol; Drug: Insulin; 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.; Other Names: HNC; Hyperinsulinemic-normoglycemic clamp
Placebo Comparator: Insulin, no protein after surgery; 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; 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.; Other Names: HNC; 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

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Canadian Institutes of Health Research (CIHR)

Publications and helpful links

General Publications

• Schricker T, Meterissian S, Wykes L, Eberhart L, Lattermann R, Carli F. Postoperative protein sparing with epidural analgesia and hypocaloric dextrose. Ann Surg. 2004 Nov;240(5):916-21. doi: 10.1097/01.sla.0000143249.93856.66.
• Schricker T, Wykes L, Carli F. Epidural blockade improves substrate utilization after surgery. Am J Physiol Endocrinol Metab. 2000 Sep;279(3):E646-53. doi: 10.1152/ajpendo.2000.279.3.E646.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: January 8, 2014
• First Submitted That Met QC Criteria: January 9, 2014
• First Posted (Estimate): January 10, 2014

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: colorectal cancer; anabolism; perioperative nutrition; hyperinsulinemia; normoglycemia; protein recovery; hyperinsulinemic-normoglycemic clamp
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Amino-acid, glucose, and electrolyte solution
• Other Study ID Numbers: 12-459-GEN