Cardiac Surgery Neuroprotection Study in Elders (CNS-Elders)

Albert Einstein College of Medicine

Status and phase: Completed; Phase 2

Conditions: Post-operative Delirium; Post-operative Cognitive Decline

Treatments: Drug: Aspart insulin; Device: Intranasal mucosal atomizer device; Drug: Normal saline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01561378

2010-538

R03AG040673 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 22 patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

22 participants in 2 patient groups, including a placebo group

Insulin

Experimental group

Description:

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

Treatment:

Device: Intranasal mucosal atomizer device

Drug: Aspart insulin

Normal saline

Placebo Comparator group

Description:

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

Treatment:

Drug: Normal saline

Device: Intranasal mucosal atomizer device