Clinical trial NCT02729064: Intraoperative Nasal Insulin Effect on Plasma and CSF Insulin Concentration and Blood Glucose
Official title: Effect of Intranasal Insulin Administration on Glycaemia and Insulin Concentrations in Plasma and Cerebrospinal Fluid During Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Ischemic Heart Disease
Aortic Aneurysm
Keywords: Intranasal Insulin
Insulin concentration
Blood glucose
Cerebro Spinal Fluid insulin
Intraoperative blood glucose
Cardiac Surgery
Thoracic Surgery
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2016-04-06
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Blood Glucose
timeFrame: During Surgery
measure: Plasma Insulin
timeFrame: During Surgery
measure: Cerebrospinal Fluid Insulin
timeFrame: During Surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Royal Victoria Hospital McGill University Health Centre
state: Quebec
Study officials:
References:
citation: 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.
citation: 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.