Cardiac Surgery Neuroprotection Study in Elders

Phase 2

Completed

• Conditions: Post-operative Cognitive Decline; Post-operative Delirium
• Interventions: Drug: Normal saline; Drug: Aspart insulin; Device: Intranasal mucosal atomizer device

• Registration Number: NCT01561378
• Lead Sponsor: Albert Einstein College of Medicine

Brief 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.

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 Timeline

• Study First Submitted: 2012-03-20
• Study First Submitted QC: 2012-03-21
• Study First Posted: 2012-03-23
• Study Start: 2012-08
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Results First Submitted: 2020-07-21
• Results First Submitted QC: 2020-10-21
• Results First Posted: 2020-10-22
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-09
• Last Update Posted: 2021-11-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Insulin	Intranasal mucosal atomizer device	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
Normal saline	Intranasal mucosal atomizer device	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
Normal saline	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
Insulin	Aspart 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

Primary Outcome Measures

Name	Time	Method
Change From Baseline Cognitive Function	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Albert Einstein College of Medicine - Montefiore Medical Center; 🇺🇸 Bronx, New York, United States