Cardiac Surgery Neuroprotection Study in Elders

Study Overview
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Brief Summary
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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
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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).

Official Title
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Intranasal Insulin for Neuroprotection in Elderly Cardiac Surgery Patients

Conditions
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Post-operative Cognitive Decline, Post-operative Delirium

Intervention / Treatment
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* Drug: Aspart insulin
* Drug: Normal saline
* Device: Intranasal mucosal atomizer device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: elderly patients (>=65 years old) undergoing elective coronary artery bypass graft and/or valve surgery requiring cardiopulmonary bypass English or Spanish-speaking Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin<br>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 | Drug: Aspart insulin<br>* 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)<br>* Other names: NovoLog;Device: Intranasal mucosal atomizer device<br>* 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.<br>* Other names: mucosal atomizer device, MAD;|
| Placebo Comparator: Normal saline<br>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 | Drug: Normal saline<br>* 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)<br>* Other names: 0.9% sodium chloride solution;Device: Intranasal mucosal atomizer device<br>* 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.<br>* Other names: mucosal atomizer device, MAD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delirium and Coma Free Days | Assessed using the Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-ICU (CAM-ICU) | 7 days | 
| Association Between Post-operative Delirium and Post-operative Cognitive Decline |  | 7 days, 6 weeks | 
| Hypoglycemia |  | 14 days | 
| Nasal Irritation |  | 14 days | 
| Survival |  | 30-day, 90-day | 
| ICU Length of Stay |  | 1 to 90 days | 
| Hospital Length of Stay |  | 1 to 90 days |