Intraoperative Nasal Insulin Effect on Plasma and CSF Insulin Concentration and Blood Glucose

Effect of Intranasal Insulin Administration on Glycaemia and Insulin Concentrations in Plasma and Cerebrospinal Fluid During Surgery

Intranasal insulin is reported to improves memory performance in patients suffering from cognitive impairment. The investigators have previously shown that intraoperative insulin administration preserves both short and long-term memory function after cardiac surgery. Applying intranasal insulin bypasses blood-brain barrier and cause elevation of insulin concentrations in the cerebrospinal fluid without major effects on peripheral insulin level. Patients undergoing major surgery are exposed to carbohydrate and insulin metabolism alteration. The goal of the study is to study the effect of intranasal insulin on blood glucose, plasma and cerebrospinal insulin concentration in patients undergoing cardiac surgery or endovascular thoracic aneurysm repair.

Study Overview

• Status: Unknown
• Conditions: Ischemic Heart Disease; Aortic Aneurysm
• Intervention / Treatment: Drug: Humulin R; Drug: Normal Saline

Detailed Description

Clinical trials have demonstrated that intranasal insulin improves both memory performance and metabolic integrity of the brain in patients suffering from Alzheimer's disease or cognitive impairment. A single dose of intranasal insulin acutely improved memory in memory-impaired older adults. Cognitive impairment in post-operative period is an increasing problem as more elderly patients undergo major surgery. The investigators have previously shown that intraoperative insulin administration while maintaining normoglycaemia preserves both short and long-term memory function after open heart surgery.

Applying insulin as a nasal spray bypasses blood-brain barrier and cause significant and sustained elevation of insulin concentrations in the cerebrospinal fluid (CSF) without major effects on peripheral insulin levels. The administration of 40 IU of intranasal insulin(INI) rapidly increases CSF insulin concentration within seven minutes, peaking after 30 minutes and remaining elevated for more than 80 minutes.

Presently it is not clear if CNS insulin plays a relevant role in controlling blood glucose in humans.

Patients undergoing major surgery are exposed to metabolic and endocrine alterations in carbohydrate, protein, and insulin metabolism, often summarized as the catabolic stress response. While the effect of intravenous insulin on glucose metabolism during surgery has been extensively studied the influence of intranasal insulin administration on intraoperative plasma insulin and blood glucose concentrations is unknown.

Goal and Objectives The goal of the present study is to study the effect of intranasal insulin on

• blood glucose and plasma insulin concentrations in patients undergoing elective cardiac surgery
• blood glucose, plasma insulin and cerebrospinal insulin concentration in patients undergoing elective endovascular thoracic aneurysm repair.

• Study Type: Interventional
• Enrollment (Anticipated): 141
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hiroaki Sato, MD., PhD.; Phone Number: 36717 +15149341934; Email: hiroaki.sato2@mcgill.ca
• Study Contact Backup: Name: Thomas Schricker, MD., PhD.; Phone Number: 34883 +15149341934; Email: thomas.schricker@mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Royal Victoria Hospital McGill University Health Centre
      • Contact: Hiroaki Sato, MD., PhD.; Phone Number: 36717 5149341934; Email: hiroaki.sato2@mcgill.ca

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:

All patients (>18 years) undergoing elective open heart surgery requiring CPB or elective endovascular thoracic aortic aneurysm repair at the RVH.

Exclusion Criteria:

1. Planned use of drugs that effect plasma glucose concentration during the first four hours of surgery.
2. Patients with allergy to insulin
3. Patients with a base line blood glucose less than 3.9 mmol/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal 40; Patients will receive 40 IU of intranasal insulin (Humulin R) via a metered nasal dispenser	Drug: Humulin R; Study subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser.
Experimental: Intranasal 80; Patients will receive 80 IU of intranasal insulin (Humulin R) via a metered nasal dispenser	Drug: Humulin R; Study subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser.
Placebo Comparator: Placebo; Patients will receive intranasal normal saline via a metered nasal dispenser	Drug: Normal Saline; Study subjects will receive intranasal placebo (normal saline) via a metered nasal dispenser.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Glucose	Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Circulating concentrations of glucose will be measured.	During Surgery
Plasma Insulin	Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Plasma insulin will be measured.	During Surgery
Cerebrospinal Fluid Insulin	Cerebrospinal Fluid will be taken every 10 to 30 minutes during the endovascular thoracic aneurysm repair surgery. Insuring concentration of Cerebrospinal fluid will be measured.	During Surgery

Collaborators and Investigators

• Sponsor: Hiroaki Sato, MD., PhD.

Publications and helpful links

General Publications

• Roque P, Nakadate Y, Sato H, Sato T, Wykes L, Kawakami A, Yokomichi H, Matsukawa T, Schricker T. Intranasal administration of 40 and 80 units of insulin does not cause hypoglycemia during cardiac surgery: a randomized controlled trial. Can J Anaesth. 2021 Jul;68(7):991-999. doi: 10.1007/s12630-021-01969-5. Epub 2021 Mar 15.
• Nakadate Y, Sato H, Roque P, Sato T, Matsukawa T, Wykes L, Kawakami A, Schricker T. Accuracy of blood glucose measurements using the NOVA StatStrip(R) glucometer during cardiac surgery: a prospective observational study. Can J Anaesth. 2019 Aug;66(8):943-952. doi: 10.1007/s12630-019-01350-7. Epub 2019 Mar 20.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: March 31, 2016
• First Submitted That Met QC Criteria: April 5, 2016
• First Posted (Estimate): April 6, 2016

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Cardiac Surgery; Intranasal Insulin; Thoracic Surgery; Blood glucose; Insulin concentration; Cerebro Spinal Fluid insulin; Intraoperative blood glucose
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Aortic Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Aneurysm; Aortic Aneurysm; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 5381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO