Post-operative Cognitive DeclinePhase 2CNS-EldersNCT01561378
Cardiac Surgery Neuroprotection Study in Elders
A Phase 2 study testing Aspart insulin, Normal saline and Intranasal mucosal atomizer device in people with Post-operative Cognitive Decline and Post-operative Delirium, run by Albert Einstein College of Medicine at 1 site in United States.
Trial summary
The goal of this study is to determine the potential ability of intranasal insulin to prevent post-operative cognitive decline and post-operative delirium in an elderly cardiac surgery population. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Post-operative Cognitive Decline, Post-operative Delirium
- What is being tested?
- Aspart insulin, Normal saline and Intranasal mucosal atomizer device
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- elderly patients (>=65 years old)
- undergoing elective coronary artery bypass graft and/or valve surgery requiring cardiopulmonary bypass
- English or Spanish-speaking
Who cannot join
- severe dementia, neurodegenerative, or psychiatric disease that prevents patient from living independently at baseline
- emergent surgery
- inability to perform cognitive testing (i.e. difficulty hearing or inability to speak)
- contraindications to intranasal administration of medication
Trial locations and contacts
1 site in 1 country.
United States1 site
Albert Einstein College of Medicine - Montefiore Medical Center
The Bronx, New York, 10467
About this study
Official title: Intranasal Insulin for Neuroprotection in Elderly Cardiac Surgery Patients
The goal of this study is to determine the potential ability of intranasal insulin to prevent post-operative cognitive decline and post-operative delirium in an elderly cardiac surgery population.
Read the detailed description
Nearly half of all intensive care unit (ICU) admissions consist of adults > 65 years old, an age group that is at high risk for developing cognitive decline and delirium in the ICU. Over 50% and 70% of critically ill cardiac surgery patients develop post-operative delirium (POD) and post-operative cognitive decline (POCD), respectively. These two forms of acute cognitive dysfunction are associated with increased mortality and poor functional recovery. While distinct conditions, POD has been associated with the subsequent development of POCD, suggesting a mechanistic link.
No proven pharmacologic treatments targeting the prevention of both POD and POCD in elderly patients exist to date. Recent data suggest that insulin administered into the central nervous system via intranasal delivery improves cognitive function in elderly patients with Alzheimer's disease and mild cognitive impairment. However, its utility in preventing POD and POCD in elderly critically ill patients has not been investigated.
The hypothesis of this study is that intranasal insulin can prevent POD and POCD in elderly critically ill patients admitted to the intensive care unit after undergoing cardiac surgery. To test this hypothesis, this randomized, placebo-controlled, double-blinded Phase II study will enroll 60 patients >= 65 years old undergoing elective coronary artery bypass graft and/or valve surgery requiring cardiopulmonary bypass, and will treat them with either 40 IU of aspart insulin or placebo intranasally before surgery and then four times a day for 7 days or until hospital discharge (whichever occurs first).
- Being tested
- Aspart insulin, Normal saline, Intranasal mucosal atomizer device
- Medical subject headings
- Emergence Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspart insulinDrug
Also called NovoLog
40 IU of aspart insulin (200 microliters per nostril) will be administered intranasally using an intranasal mucosal atomizer device within 2 hours prior to surgery, and then four times a day for 7 days or until hospital discharge (whichever occurs first)
Normal salineDrug
Also called 0.9% sodium chloride solution
200 microliters of normal saline will be administered per nostril using an intranasal mucosal atomizer device within 2 hours prior to surgery, and then four times a day for 7 days or until hospital discharge (whichever occurs first)
Intranasal mucosal atomizer deviceDevice
Also called mucosal atomizer device, MAD
Insulin and placebo will be drawn into identical syringes. Nurses will administer the insulin or placebo by connecting the mucosal atomizer device (MAD) to the syringe, placing the MAD tip in the nostril and compressing the syringe plunger to spray atomized solution into the nasal cavity.
| Study group | Role | What they receive |
|---|---|---|
| Insulin | Experimental | Aspart Insulin 40 IU intranasal spray via intranasal mucosal atomizer device, four times a day for 7 days or until hospital discharge, whichever occurs first Receives: Drug: Aspart insulin; Device: Intranasal mucosal atomizer device |
| Normal saline | Placebo comparator | Normal saline (0.9% sodium chloride solution) intranasal spray via intranasal mucosal atomizer device, four times a day for 7 days or until hospital discharge, whichever occurs first Receives: Drug: Normal saline; Device: Intranasal mucosal atomizer device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline Cognitive Function
Assessed using a battery of cognitive tests which test the following four domains: 1) executive function, 2) verbal memory, 3) attention and concentration, 4) language. Cognitive testing will be performed at the following time points: baseline (1-2 weeks prior to surgery) and 6 weeks after discharge.
Measured: 6-weeks
Secondary outcomes (7)
Delirium and Coma Free Days
Assessed using the Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-ICU (CAM-ICU)
Measured: 7 days
Association Between Post-operative Delirium and Post-operative Cognitive Decline
Measured: 7 days, 6 weeks
Hypoglycemia
Measured: 14 days
Nasal Irritation
Measured: 14 days
Survival
Measured: 30-day, 90-day
ICU Length of Stay
Measured: 1 to 90 days
Hospital Length of Stay
Measured: 1 to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2012 (estimated)
- Study startAug 2012
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Post-operative Cognitive DeclineStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Shi-jun Jean Hsieh, MD, Principal investigator, Albert Einstein College of Medicine Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01561378
- Sponsor's protocol ID
- 2010-538
- Other IDs
- R03AG040673
- Acronym
- CNS-Elders
- Status last verified
- Nov 2021
- First submitted
- 20 Mar 2012
- Last updated
- 10 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Insulin for Neuroprotection in Elderly Cardiac Surgery Patients
- ClinicalTrials.gov ID
- NCT01561378
- Acronym / sponsor ID
- CNS-Elders / 2010-538
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Albert Einstein College of MedicineUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Aug 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 23 Mar 2012 (estimated)
- Results
- Posted 22 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to determine the potential ability of intranasal insulin to prevent post-operative cognitive decline and post-operative delirium in an elderly cardiac surgery population.
Detailed description
Nearly half of all intensive care unit (ICU) admissions consist of adults > 65 years old, an age group that is at high risk for developing cognitive decline and delirium in the ICU. Over 50% and 70% of critically ill cardiac surgery patients develop post-operative delirium (POD) and post-operative cognitive decline (POCD), respectively. These two forms of acute cognitive dysfunction are associated with increased mortality and poor functional recovery. While distinct conditions, POD has been associated with the subsequent development of POCD, suggesting a mechanistic link.
No proven pharmacologic treatments targeting the prevention of both POD and POCD in elderly patients exist to date. Recent data suggest that insulin administered into the central nervous system via intranasal delivery improves cognitive function in elderly patients with Alzheimer's disease and mild cognitive impairment. However, its utility in preventing POD and POCD in elderly critically ill patients has not been investigated.
The hypothesis of this study is that intranasal insulin can prevent POD and POCD in elderly critically ill patients admitted to the intensive care unit after undergoing cardiac surgery. To test this hypothesis, this randomized, placebo-controlled, double-blinded Phase II study will enroll 60 patients >= 65 years old undergoing elective coronary artery bypass graft and/or valve surgery requiring cardiopulmonary bypass, and will treat them with either 40 IU of aspart insulin or placebo intranasally before surgery and then four times a day for 7 days or until hospital discharge (whichever occurs first).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin | Experimental | Drug: Aspart insulin, Device: Intranasal mucosal atomizer deviceAspart Insulin 40 IU intranasal spray via intranasal mucosal atomizer device, four times a day for 7 days or until hospital discharge, whichever occurs first |
| Normal saline | Placebo comparator | Drug: Normal saline, Device: Intranasal mucosal atomizer deviceNormal saline (0.9% sodium chloride solution) intranasal spray via intranasal mucosal atomizer device, four times a day for 7 days or until hospital discharge, whichever occurs first |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- elderly patients (>=65 years old)
- undergoing elective coronary artery bypass graft and/or valve surgery requiring cardiopulmonary bypass
- English or Spanish-speaking
Key exclusion criteria (4 listed)
- severe dementia, neurodegenerative, or psychiatric disease that prevents patient from living independently at baseline
- emergent surgery
- inability to perform cognitive testing (i.e. difficulty hearing or inability to speak)
- contraindications to intranasal administration of medication
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 |
|---|---|---|
| Aspart insulinAlso: NovoLog40 IU of aspart insulin (200 microliters per nostril) will be administered intranasally using an intranasal mucosal atomizer device within 2 hours prior to surgery, and then four times a day for 7 days or until hospital discharge (whichever occurs first) | Drug | Insulin |
| Normal salineAlso: 0.9% sodium chloride solution200 microliters of normal saline will be administered per nostril using an intranasal mucosal atomizer device within 2 hours prior to surgery, and then four times a day for 7 days or until hospital discharge (whichever occurs first) | Drug | Normal saline |
| Intranasal mucosal atomizer deviceAlso: mucosal atomizer device, MADInsulin and placebo will be drawn into identical syringes. Nurses will administer the insulin or placebo by connecting the mucosal atomizer device (MAD) to the syringe, placing the MAD tip in the nostril and compressing the syringe plunger to spray atomized solution into the nasal cavity. | Device | Insulin, Normal saline |
Primary outcome
Change From Baseline Cognitive Function
Time frame: 6-weeks
Assessed using a battery of cognitive tests which test the following four domains: 1) executive function, 2) verbal memory, 3) attention and concentration, 4) language. Cognitive testing will be performed at the following time points: baseline (1-2 weeks prior to surgery) and 6 weeks after discharge.
7 secondary outcomes
Delirium and Coma Free Days
Time frame: 7 days
Association Between Post-operative Delirium and Post-operative Cognitive Decline
Time frame: 7 days, 6 weeks
Hypoglycemia
Time frame: 14 days
Nasal Irritation
Time frame: 14 days
Survival
Time frame: 30-day, 90-day
ICU Length of Stay
Time frame: 1 to 90 days
Hospital Length of Stay
Time frame: 1 to 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Prospective Observational Multimodal Neuromonitoring During High-Risk Adult Surgery
Postoperative Cognitive Complications, Delirium
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Postsurgical Pain and Opioid Use in Older Adults: Effects of Mild Cognitive Impairment
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Post Operative Cognitive Dysfunction After Oncologic Surgery
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Impact of Preoperative Mild Cognitive Impairment on Postoperative Delirium in Patients Undergoing Cardiac Surgery
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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.
Shi-jun Jean Hsieh, MD principal investigator
Albert Einstein College of Medicine Montefiore Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aspart insulin, Normal saline and Intranasal mucosal atomizer device in people with Post-operative Cognitive Decline and Post-operative Delirium, run by Albert Einstein College of Medicine at 1 site in United States.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 10 Nov 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline Cognitive Function (time frame: 6-weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Nov 2021.