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

• Sponsor: Robert Silbergleit (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05062785
• Collaborator: American Heart Association (Other)
• Enrollment: 24
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 23.9
• Patients Per Site Per Month: 1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Out-Of-Hospital Cardiac Arrest; Healthy	Drug: Intranasal insulin	Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention 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.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)
• Primary Purpose: Treatment
• Official Title: Phase 1, Open Label Dose-Finding Study of Intranasal Insulin in Healthy Participants
• Actual Study Start Date: Oct 4, 2021
• Anticipated Primary Completion Date: Oct 1, 2023
• Anticipated Study Completion Date: Oct 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Severe Hypoglycemia as defined by blood glucose < 45 milligrams per deciliter (mg/dL) [Up to 4 hours after drug administration]

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

Secondary Outcome Measures

1. Change in blood glucose [Baseline, up to 4 hours after drug administration]

2. Change in serum insulin [Baseline, up to 4 hours after drug administration]

3. Change in serum C-peptide levels [Baseline, up to 4 hours after drug administration]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• Robert Silbergleit
• American Heart Association

Investigators

• Principal Investigator: Robert Silbergleit, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Silbergleit, Professor of Emergency Medicine, University of Michigan
• ClinicalTrials.gov Identifier: NCT05062785
• Other Study ID Numbers: HUM00171279
• First Posted: Sep 30, 2021
• Last Update Posted: Nov 9, 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
• Keywords provided by Robert Silbergleit, Professor of Emergency Medicine, University of Michigan: Healthy participants; intranasal insulin
• Additional relevant MeSH terms: Out-of-Hospital Cardiac Arrest; Insulin; Insulin, Globin Zinc

Study Results

No Results Posted as of Nov 9, 2021