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

Phase 1

• Conditions: Ischemic Heart Disease; Aortic Aneurysm
• Interventions: Drug: Normal Saline; Drug: Humulin R

• Registration Number: NCT02729064
• Lead Sponsor: Hiroaki Sato, MD., PhD.

Brief 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.

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 Timeline

• Study First Submitted: 2016-03-31
• Study First Submitted QC: 2016-04-05
• Study First Posted: 2016-04-06
• Study Start: 2016-09
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-23
• Last Update Posted: 2021-02-24
• Primary Completion: 2021-09
• Study Completion: 2021-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 141

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Normal Saline	Patients will receive intranasal normal saline via a metered nasal dispenser
Intranasal 40	Humulin R	Patients will receive 40 IU of intranasal insulin (Humulin R) via a metered nasal dispenser
Intranasal 80	Humulin R	Patients will receive 80 IU of intranasal insulin (Humulin R) via a metered nasal dispenser

Primary Outcome Measures

Name	Time	Method
Cerebrospinal Fluid Insulin	During Surgery	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.
Blood Glucose	During Surgery	Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Circulating concentrations of glucose will be measured.
Plasma Insulin	During Surgery	Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Plasma insulin will be measured.

Trial Locations

Locations (1)

Royal Victoria Hospital McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada