The Effect of Insulin on Protein Metabolism After Cardiac Surgery

NCT ID: NCT01601561

Last Updated: 2012-05-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30

Brief Summary

Background: The hyperinsulinemic-normoglycaemic clamp technique is a precise method of providing insulin and glucose while maintaining normoglycemia. High-dose insulin has profound effects on glucose and protein metabolism. It has been demonstrated in coronary artery bypass graft (CABG) surgery patients that high-dose insulin causes hypoaminoacidaemia. The investigators hypothesize that the reduction of plasma amino acids (AAs) levels as seen in patients undergoing CABG surgery and receiving high-dose insulin is a consequence of an inhibition of whole body proteolysis as assessed by L-[1-13C]leucine tracer kinetics.

Objective: The present study aims to investigate the effect of high-dose insulin therapy on whole body protein, glucose and end-organ metabolism in patients undergoing CABG surgery using stable isotope tracers [6,6-2H2]glucose, L-[1-13C]-leucine and L-[2H5]phenylalanine. The changes in the metabolic-endocrine milieu will also be evaluated by plasma concentrations of glucose, lactate, free fatty acids, prealbumin, albumin, fibrinogen, insulin, glucagon, and cortisol.

Methods: With the approval of local institution's ethical committee, 30 patients scheduled for elective will be enrolled. The patients will be divided randomly into two groups. The control group will receive a standard IV insulin protocol with the aim of keeping blood glucose < 10 mmol/L. The treatment group will be administered a high dose insulin infusion of 5 mU/kg/min coupled with a variable infusion of glucose to maintain normoglycemia (4-6 mmol/L). Insulin infusion will be continued until the end of the study period approximately 8 hours after surgery. L-[1-13C]leucine and [6,6-2H2]glucose kinetics will be used to assess changes in whole body protein and glucose kinetics. Hepatic albumin synthesis will be determined by using primed continuous infusion of L-[2H5]phenylalanine. The preoperative measurements will be performed on the morning before the surgery. Postoperative studies will be conducted two hours after arrival in the intensive care unit. Tracer kinetics between the two groups will be analyzed using ANOVA for repeated measurements.

Significance: High-dose-insulin results in a significant reduction in plasma AAs in cardiac surgery. This study should address if this drop in plasma AA levels is secondary to a decrease in breakdown, an increase in synthesis or both during high-dose insulin therapy in open heart surgery.

Conditions

Cardiac Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

High-dose insulin

Group Type: EXPERIMENTAL

Regular human insulin injection

Intervention Type: DRUG

Hyperinsulinemic normoglycemic clamp from beginning of surgery until 8 hours after surgery.

Humulin R 5 mU/kg/min and a variable infusion of glucose.

Control

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Regular human insulin injection

Hyperinsulinemic normoglycemic clamp from beginning of surgery until 8 hours after surgery.

Humulin R 5 mU/kg/min and a variable infusion of glucose.

Intervention Type: DRUG

Other Intervention Names

Humulin R

Eligibility Criteria

Inclusion Criteria

• ability to give informed consent

Exclusion Criteria

• signs of severe malnutrition or obesity: body mass index (BMI) < 20 or > 30 kg.m-2, more than 10% involuntary body weight loss over the preceding six months, serum albumin < 35 g.L-1
• chronic liver failure

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roupen Hatzakorzian, MD

Role: PRINCIPAL_INVESTIGATOR

McGill University Health Centre/Research Institute of the McGill University Health Centre

Locations

Royal Victoria Hospital, McGill University Health Centre

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Facility Contacts

Roupen Hatzakorzian, MD

Role: primary

roupenhatz@hotmail.com

514 934 1934 ext. 31104

Thomas Schricker, MD PhD

Role: backup

thomas.schricker@mcgill.ca

514 934 1934 ext. 36057

Other Identifiers

09-105-SDR

Identifier Type: -

Identifier Source: org_study_id