Post-operative Cognitive Decline, Post-operative Delirium
Conditions
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).
Interventions
DRUGNormal 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)
DEVICEIntranasal 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.
DRUGAspart 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)
Sponsors
National Institute on Aging (NIA)
Albert Einstein College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Delirium and Coma Free Days | 7 days | Assessed using the Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-ICU (CAM-ICU) |
| Association Between Post-operative Delirium and Post-operative Cognitive Decline | 7 days, 6 weeks | — |
| Hypoglycemia | 14 days | — |
| Hospital Length of Stay | 1 to 90 days | — |
| Survival | 30-day, 90-day | — |
| ICU Length of Stay | 1 to 90 days | — |
| Nasal Irritation | 14 days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
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)
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. | 0 |
| 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
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)
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. | 0 |
| Total | 0 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: 6-weeks
Population: The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available
Secondary
Association Between Post-operative Delirium and Post-operative Cognitive Decline
Time frame: 7 days, 6 weeks
Population: The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available
Secondary
Delirium and Coma Free Days
Assessed using the Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-ICU (CAM-ICU)
Time frame: 7 days
Population: The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available
Secondary
Hospital Length of Stay
Time frame: 1 to 90 days
Population: The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available
Secondary
Hypoglycemia
Time frame: 14 days
Population: The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available
Secondary
ICU Length of Stay
Time frame: 1 to 90 days
Population: The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available
Secondary
Nasal Irritation
Time frame: 14 days
Population: The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available
Secondary
Survival
Time frame: 30-day, 90-day
Population: The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available