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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ischemic Heart Disease, Aortic Aneurysm

Intervention / Treatment
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* Drug: Humulin R
* Drug: Normal Saline


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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intranasal Insulin, Insulin concentration, Blood glucose, Cerebro Spinal Fluid insulin, Intraoperative blood glucose, Cardiac Surgery, Thoracic Surgery