Ischemic Heart DiseasePhase 1NCT02729064
Intraoperative Nasal Insulin Effect on Plasma and CSF Insulin Concentration and Blood Glucose
A Phase 1 study testing Humulin R and Normal Saline in people with Ischemic Heart Disease and Aortic Aneurysm, run by Hiroaki Sato, MD., PhD. at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Heart Disease, Aortic Aneurysm
- What is being tested?
- Humulin R and Normal Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 141 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2016to Sep 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients (>18 years) undergoing elective open heart surgery requiring CPB or elective endovascular thoracic aortic aneurysm repair at the RVH.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Royal Victoria Hospital McGill University Health Centre
Montreal, Quebec, H4A 3J1
Hiroaki Sato, MD., PhD., 5149341934 ext. 36717, hiroaki.sato2@mcgill.ca
About this study
Official title: Effect of Intranasal Insulin Administration on Glycaemia and Insulin Concentrations in Plasma and Cerebrospinal Fluid During Surgery
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.
Read the 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.
- Conditions
- Ischemic Heart Disease, Aortic Aneurysm
- Being tested
- Humulin R, Normal Saline
- Keywords
- Intranasal Insulin, Insulin concentration, Blood glucose, Cerebro Spinal Fluid insulin, Intraoperative blood glucose, Cardiac Surgery, Thoracic Surgery
- Medical subject headings
- Myocardial Ischemia, Aortic Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Humulin RDrug
Study subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser.
Normal SalineDrug
Study subjects will receive intranasal placebo (normal saline) via a metered nasal dispenser.
| Study group | Role | What they receive |
|---|---|---|
| Intranasal 40 | Experimental | Patients will receive 40 IU of intranasal insulin (Humulin R) via a metered nasal dispenser Receives: Drug: Humulin R |
| Intranasal 80 | Experimental | Patients will receive 80 IU of intranasal insulin (Humulin R) via a metered nasal dispenser Receives: Drug: Humulin R |
| Placebo | Placebo comparator | Patients will receive intranasal normal saline via a metered nasal dispenser Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Glucose
Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Circulating concentrations of glucose will be measured.
Measured: During Surgery
Plasma Insulin
Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Plasma insulin will be measured.
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.
Measured: During Surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study startSep 2016
- Primary completionSep 2021 (estimated)
- Study completionSep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemic Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 141 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hiroaki Sato, MD., PhD.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Hiroaki Sato, MD., PhD., McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02729064
- Sponsor's protocol ID
- 5381
- Status last verified
- Feb 2021
- First submitted
- 31 Mar 2016
- Last updated
- 24 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 33721199Nakadate 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.
PubMed 30895515
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intranasal Insulin Administration on Glycaemia and Insulin Concentrations in Plasma and Cerebrospinal Fluid During Surgery
- ClinicalTrials.gov ID
- NCT02729064
- Acronym / sponsor ID
- 5381
- Conditions
- Ischemic Heart Disease, Aortic Aneurysm
- Keywords
- Intranasal Insulin, Insulin concentration, Blood glucose, Cerebro Spinal Fluid insulin, Intraoperative blood glucose, Cardiac Surgery, Thoracic Surgery
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 141 participants (estimated)
- Lead sponsor
- Hiroaki Sato, MD., PhD.University, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- Sep 2021 (estimated)
- Study completion
- Sep 2021 (estimated)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Intranasal 40 | Experimental | Drug: Humulin RPatients will receive 40 IU of intranasal insulin (Humulin R) via a metered nasal dispenser |
| Intranasal 80 | Experimental | Drug: Humulin RPatients will receive 80 IU of intranasal insulin (Humulin R) via a metered nasal dispenser |
| Placebo | Placebo comparator | Drug: Normal SalinePatients will receive intranasal normal saline via a metered nasal dispenser |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients (>18 years) undergoing elective open heart surgery requiring CPB or elective endovascular thoracic aortic aneurysm repair at the RVH.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Humulin RStudy subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser. | Drug | Intranasal 40, Intranasal 80 |
| Normal SalineStudy subjects will receive intranasal placebo (normal saline) via a metered nasal dispenser. | Drug | Placebo |
Primary outcome
Blood Glucose
Time frame: 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
Time frame: During Surgery
Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Plasma insulin will be measured.
Cerebrospinal Fluid Insulin
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2021.
- Derived from this study: PubMed 33721199Roque 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.
- Derived from this study: PubMed 30895515Nakadate 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Humulin R and Normal Saline in people with Ischemic Heart Disease and Aortic Aneurysm, run by Hiroaki Sato, MD., PhD. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hiroaki Sato, MD., PhD. (+15149341934 ext. 36717, hiroaki.sato2@mcgill.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Glucose (time frame: During Surgery). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02729064, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2021.