Back to results

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

Primary Purpose

Out-Of-Hospital Cardiac Arrest, Healthy

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Intranasal insulin

About this trial

This is an interventional treatment trial for Out-Of-Hospital Cardiac Arrest focused on measuring Healthy participants, intranasal insulin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

University of Michigan

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intranasal insulin

Arm Description

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

Outcomes

Primary Outcome Measures

Severe Hypoglycemia as defined by blood glucose < 45 milligrams per deciliter (mg/dL)

Severe Hypoglycemia will be considered a dose limiting toxicity (DLT).

Secondary Outcome Measures

Change in blood glucose

Change in serum insulin

Change in serum C-peptide levels

Full Information

NCT ID

NCT05062785

First Posted

September 20, 2021

Last Updated

October 13, 2022

Sponsor

Robert Silbergleit

Collaborators

American Heart Association

1. Study Identification

Unique Protocol Identification Number

NCT05062785

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

October 4, 2021 (Actual)

Primary Completion Date

April 25, 2022 (Actual)

Study Completion Date

April 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Robert Silbergleit

Collaborators

American Heart Association

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Out-Of-Hospital Cardiac Arrest, Healthy

Keywords

Healthy participants, intranasal insulin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

For every 6 participants, iterations of a Bayesian model will be performed to associate the administered dose with the frequency of dose-limiting hypoglycemia or other adverse events. The model will adaptively reallocate the dose increments for the next 6 participants. To provide more precise and reproducible estimates of dose-limiting toxicity, the trial will modify the size of dose increments based on the developing model to allocate more administrations to areas of the model with greatest uncertainty, or to higher doses in the absence of dose-limiting hypoglycemia.

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intranasal insulin

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Intranasal insulin

Other Intervention Name(s)

HUMULIN R U-500

Intervention Description

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.

Primary Outcome Measure Information:

Title

Severe Hypoglycemia as defined by blood glucose < 45 milligrams per deciliter (mg/dL)

Description

Severe Hypoglycemia will be considered a dose limiting toxicity (DLT).

Time Frame

Up to 4 hours after drug administration

Secondary Outcome Measure Information:

Title

Change in blood glucose

Time Frame

Baseline, up to 4 hours after drug administration

Title

Change in serum insulin

Time Frame

Baseline, up to 4 hours after drug administration

Title

Change in serum C-peptide levels

Time Frame

Baseline, up to 4 hours after drug administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert Silbergleit, MD

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs