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

Ischemic Heart Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02729064
• Other study ID #: 5381
• Status: Recruiting
• Phase: Phase 1
• Start date: September 2016
• Est. completion date: September 2021

Study information

• Verified date: February 2021
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: Hiroaki Sato, MD., PhD.
• Phone: +15149341934
• Email: hiroaki.sato2[@]mcgill.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 141
• Est. completion date: September 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm
• Aortic Aneurysm
• Coronary Artery Disease
• Heart Diseases
• Ischemic Heart Disease
• Myocardial Ischemia

Intervention

Drug:
• Humulin R
Study subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser.
• Normal Saline
Study subjects will receive intranasal placebo (normal saline) via a metered nasal dispenser.

Locations

Country	Name	City	State
Canada	Royal Victoria Hospital McGill University Health Centre	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Hiroaki Sato, MD., PhD.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Plasma Insulin	Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Plasma insulin will be measured.	During Surgery
Primary	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