Cardiac Surgery Neuroprotection Study in Elders (CNS-Elders)

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.

Study Overview

• Status: Completed
• Conditions: Post-operative Delirium; Post-operative Cognitive Decline
• Intervention / Treatment: Drug: Aspart insulin; Device: Intranasal mucosal atomizer device; Drug: Normal saline

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Albert Einstein College of Medicine - Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. elderly patients (>=65 years old)
2. undergoing elective coronary artery bypass graft and/or valve surgery requiring cardiopulmonary bypass
3. English or Spanish-speaking

Exclusion Criteria:

1. severe dementia, neurodegenerative, or psychiatric disease that prevents patient from living independently at baseline
2. emergent surgery
3. inability to perform cognitive testing (i.e. difficulty hearing or inability to speak)
4. contraindications to intranasal administration of medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Insulin; 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; 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); Other Names: NovoLog; Device: Intranasal mucosal atomizer device; 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.; Other Names: mucosal atomizer device, MAD
PLACEBO_COMPARATOR: Normal saline; 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	Device: Intranasal mucosal atomizer device; 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.; Other Names: mucosal atomizer device, MAD; Drug: Normal saline; 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); Other Names: 0.9% sodium chloride solution

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Shi-jun Jean Hsieh, MD, Albert Einstein College of Medicine - Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (ESTIMATE): March 23, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 10, 2021
• Last Update Submitted That Met QC Criteria: November 9, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Aspart
• Other Study ID Numbers: 2010-538; R03AG040673 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No