Dose-Finding Study of Intranasal Insulin in Healthy Participants Insulin in Healthy Participants

Phase 1, Open Label Dose-Finding Study of Intranasal Insulin in Healthy Participants

This study is to determine the safety and tolerability of regular insulin (Humulin R) when given intranasally (as drops in nostrils).

Healthy participants will be enrolled to determine the maximum tolerated dose of intranasal insulin.

Study Overview

• Status: Completed
• Conditions: Healthy; Out-Of-Hospital Cardiac Arrest
• Intervention / Treatment: Drug: Intranasal insulin

Detailed Description

This is being studied because intranasal insulin may be a way to prevent the brain injury that occurs after a cardiac arrest. Cardiac arrest is a life-threatening condition in which the heart suddenly stops beating and there is no blood flow to the body. If cardiac arrest is not treated immediately, it causes sudden death. Even when immediate treatment gets the heart beating again, many victims remain comatose and die later from brain injury. Nasal insulin, given immediately after a cardiac arrest may prevent or reduce brain injury. Nasal insulin reduces brain injury in animal experiments, and has been used to try to improve brain degeneration in patients with Alzheimer's disease. However, cardiac arrest patients may need higher doses than patients with Alzheimer's disease, therefore, this study is to examine those higher doses.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Good health based on medical history, physical exam, and routine laboratory testing.
• Female participants must have negative urine pregnancy test or be surgically sterilized or postmenopausal. Criteria for menopause are surgical menopause (hysterectomy, oophorectomy) or age > 45 years with the absence of menses for greater than 12 months. Tubal ligation with menses within the past 12 months is not considered to be surgical sterilization.
• Body mass index (BMI) between 18 kilogram / square meter (kg/m2) and 35 kg/m2.
• Willing and able to stay at the clinical research facility as required by the protocol
• Willing and able to comply with the investigational nature of the study and able to communicate well with investigators
• Ability to comprehend and willing to provide written informed consent in accordance with institutional and regulatory guidelines

Exclusion Criteria:

• Known allergy to insulin.
• Preexisting diabetes.
• Current or previous use of diabetes medication or insulin.
• Any nasal disease or congestion that may interfere with intranasal drug absorption.
• Baseline hypoglycemia (blood glucose ≤ 65 mg/dL) or hyperglycemia (blood glucose > 200 mg/dL) as evident from the screening labs.
• Active serious disease, such as liver disease, kidney disease, uncontrolled hypertension, clinically significant hypokalemia, and significant or unstable medical illness
• Blood donation in excess of 500 milliliter (mL) within 60 days prior to the first dose of study medication.
• Treated with an investigational drug within 30 days.
• Individuals with inadequate venous access.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intranasal insulin; A total of 11 possible doses will be tested, ranging from 0 to 1000 U insulin.

Drug: Intranasal insulin; This will be given intranasally at differing doses depending on study day. A total of 11 possible doses will be tested, ranging from 0 to 1000 U insulin. Each volunteer will come for 5 visits. On the first treatment day participants will receive placebo (sterile water) in each nostril followed by a 4-hour observation period. After this observation period participants will receive the initial dose of insulin squirted in each nostril followed by a a 4 hour observation period. Participants will have at least 7 days in between the other 4 visits. Subsequent visits will include increased doses of insulin (depending on how this is tolerated) and will take approximately 4 hours at these visits.; Other Names: HUMULIN R U-500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe Hypoglycemia	Results reflect the participants who experienced severe hypoglycemia generically at the time they received a dose of insulin, as defined by blood glucose < 45 milligrams per deciliter (mg/dL). Severe hypoglycemia was considered a dose limiting toxicity (DLT).	Within 4 hours of dosing during each of 5 visits

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood Glucose - Study Visit 1 (100 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline and up to 4 hours after drug administration (Study Visit 1, Day 1)
Change in Blood Glucose - Study Visit 1 (200 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Blood Glucose - Study Visit 1 (400 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Blood Glucose - Study Visit 2 (400 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Blood Glucose - Study Visit 2 (600 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Blood Glucose - Study Visit 3 (600 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Blood Glucose - Study Visit 3 (800 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Blood Glucose - Study Visit 4 (800 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Blood Glucose - Study Visit 4 (900 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Blood Glucose - Study Visit 5 (1000 Units)	Change in participant blood glucose from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. Higher numbers indicated a higher level of blood glucose. This procedure was followed at each study visit.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 1 (100 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study visit. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 1 (200 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study visit. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 1 (400 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study visit. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 2 (400 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 2 (600 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 3 (600 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 3 (800 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 4 (800 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 4 (900 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum C-peptide Levels - Study Visit 5 (1000 Units)	Change in participant C-peptide Levels from baseline as measured by blood draws taken at 15-minute and 30-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study. C-peptide levels in the blood indicate how much insulin the pancreas is producing. Lower C-peptide levels suggest the body is producing little or no insulin, while higher C-peptide levels may indicate insulin resistance.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 1 (100 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 1 (200 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 1 (400 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 2 (400 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 2 (600 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 3 (600 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 3 (800 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 4 (800 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 4 (900 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration
Change in Serum Insulin - Study Visit 5 (1000 Units)	Serum insulin refers to the measurement of insulin levels in the blood. Change in participant serum insulin from baseline as measured by blood draws taken at 15-minute, 30-minute, and 60-minute intervals following administration of intra-nasal insulin. This procedure was followed at each study.	Baseline, up to 4 hours after drug administration

Collaborators and Investigators

• Sponsor: Robert Silbergleit
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Robert Silbergleit, MD, University of Michigan

Publications and helpful links

Helpful Links

• Link to a complete de-identified participant-level dataset archived in the University of Michigan Deep Blue Repository consistent with the Open Science standards of the American Heart Society

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2021
• Primary Completion (Actual): April 25, 2022
• Study Completion (Actual): April 25, 2022

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: September 20, 2021
• First Posted (Actual): September 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Healthy participants; intranasal insulin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: HUM00171279

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