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

NCT ID: NCT02729064

Last Updated: 2021-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

141 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2021-09-30

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.

Conditions

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Ischemic Heart Disease Aortic Aneurysm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Intranasal 40

Patients will receive 40 IU of intranasal insulin (Humulin R) via a metered nasal dispenser

Group Type EXPERIMENTAL

Humulin R

Intervention Type DRUG

Study subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser.

Intranasal 80

Patients will receive 80 IU of intranasal insulin (Humulin R) via a metered nasal dispenser

Group Type EXPERIMENTAL

Humulin R

Intervention Type DRUG

Study subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser.

Placebo

Patients will receive intranasal normal saline via a metered nasal dispenser

Group Type PLACEBO_COMPARATOR

Normal Saline

Intervention Type DRUG

Study subjects will receive intranasal placebo (normal saline) via a metered nasal dispenser.

Interventions

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Humulin R

Study subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser.

Intervention Type DRUG

Normal Saline

Study subjects will receive intranasal placebo (normal saline) via a metered nasal dispenser.

Intervention Type DRUG

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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hiroaki Sato, MD., PhD.

OTHER

Sponsor Role lead

Responsible Party

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Hiroaki Sato, MD., PhD.

Assistant Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Royal Victoria Hospital McGill University Health Centre

Montreal, Quebec, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Hiroaki Sato, MD., PhD.

Role: CONTACT

+15149341934 ext. 36717

Thomas Schricker, MD., PhD.

Role: CONTACT

+15149341934 ext. 34883

Facility Contacts

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Hiroaki Sato, MD., PhD.

Role: primary

5149341934 ext. 36717

References

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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.

Reference Type DERIVED
PMID: 33721199 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30895515 (View on PubMed)

Other Identifiers

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5381

Identifier Type: -

Identifier Source: org_study_id

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