CNS-Elders: Cardiac Surgery Neuroprotection Study in Elders

• Sponsor: Albert Einstein College of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01561378
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 26
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Post-operative Cognitive Decline; Post-operative Delirium	Drug: Aspart insulin; Drug: Normal saline; Device: Intranasal mucosal atomizer device	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Intranasal Insulin for Neuroprotection in Elderly Cardiac Surgery Patients
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

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	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 ; 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

Outcome Measures

Primary Outcome Measures

1. 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

1. Delirium and Coma Free Days [7 days]

   Assessed using the Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-ICU (CAM-ICU)

2. Association Between Post-operative Delirium and Post-operative Cognitive Decline [7 days, 6 weeks]

3. Hypoglycemia [14 days]

4. Nasal Irritation [14 days]

5. Survival [30-day, 90-day]

6. ICU Length of Stay [1 to 90 days]

7. Hospital Length of Stay [1 to 90 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Einstein College of Medicine - Montefiore Medical Center	Bronx	New York	United States	10467

Sponsors and Collaborators

• Albert Einstein College of Medicine
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Shi-jun Jean Hsieh, MD, Albert Einstein College of Medicine - Montefiore Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT01561378
• Other Study ID Numbers: 2010-538; R03AG040673
• First Posted: Mar 23, 2012
• Last Update Posted: Nov 10, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Delirium; Cognitive Dysfunction; Insulin Aspart

Study Results

Participant Flow

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Period Title: Overall Study
STARTED	11	11
COMPLETED	11	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Insulin	Normal Saline	Total
Arm/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 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.	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.	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age (years) []
Sex: Female, Male () []
Female
Male
Race and Ethnicity Not Collected () []

Outcome Measures

1. Primary Outcome

Title	Change From Baseline Cognitive Function
Description	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

Outcome Measure Data

Analysis Population Description

The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Measure Participants	0	0

2. Secondary Outcome

Title	Delirium and Coma Free Days
Description	Assessed using the Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-ICU (CAM-ICU)
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Measure Participants	0	0

3. Secondary Outcome

Title	Association Between Post-operative Delirium and Post-operative Cognitive Decline
Time Frame	7 days, 6 weeks

Outcome Measure Data

Analysis Population Description

The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Hypoglycemia
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Measure Participants	0	0

5. Secondary Outcome

Title	Nasal Irritation
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Measure Participants	0	0

6. Secondary Outcome

Title	Survival
Time Frame	30-day, 90-day

Outcome Measure Data

Analysis Population Description

The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Measure Participants	0	0

7. Secondary Outcome

Title	ICU Length of Stay
Time Frame	1 to 90 days

Outcome Measure Data

Analysis Population Description

The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Measure Participants	0	0

8. Secondary Outcome

Title	Hospital Length of Stay
Time Frame	1 to 90 days

Outcome Measure Data

Analysis Population Description

The PI has left the institution. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available

Arm/Group Title	Insulin	Normal Saline
Arm/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 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.	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.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The PI has left the institution. Efforts were made to contact the PI/study team members on several occasions, but were unsuccessful. No study or adverse event data are available
Arm/Group Title	Insulin		Normal Saline
Arm/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 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.		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.
All Cause Mortality
	Insulin		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Insulin		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Insulin		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

The PI has left the institution. Efforts were made to contact the PI/study team members on several occasions, but were unsuccessful. Besides the amount of patients accrued to each arm/group, no study or adverse event data are available.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.