Dose-Dependent Effect of Intranasal Insulin in Humans Using Functional Magnetic Resonance Imaging (fMRI)

Phase 1, Dose-Dependent Effect of Intranasal Insulin in Humans Using Functional MRI

The purpose of this trial is to study the brain response using functional MRI (fMRI) before and after varying doses of insulin given through the nose. The magnetic resonance imaging uses a very strong magnet to produce images of participant's brain. It becomes a functional MRI when the study team looks at the activity within the brain (blood flow / change in metabolism).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Intranasal insulin

Detailed Description

If cardiac arrest is not treated immediately, it causes sudden death. Intranasal insulin may be a way to prevent the brain injury that occurs after a cardiac arrest or other brain injury. Even when immediate treatment gets the heart beating again, many victims remain comatose and die later from 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 in doses up to 160 units.

• Study Type: Interventional
• Enrollment (Actual): 6
• 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: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants in good health based on medical history, physical exam, and routine laboratory testing
• Female participants must have a 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.
• Body mass index (BMI) between 18 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
• Ability to lie flat for a minimum of 2-hours

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 milligrams per deciliter (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
• Treated with an investigational drug within 30 days.
• Individuals with inadequate venous access.
• Claustrophobic, uncontrollable shaking, or unable to lie still for a lengthy period.
• Any metals or implanted devices within the body.
• Any foreign metallic objects in the body.
• Females that are pregnant, trying to become pregnant, or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intranasal insulin and placebo; A total of 3 possible doses will be tested of insulin 0 units (u) (placebo (diluent), 500u, and 1000u. The order that participants will receive these doses will be in a random order.

Drug: Intranasal insulin; Enrolled Participants for this trial will come for 3 study visits. The doses will be administered in varying order: participants will be randomized to one six possible permutations of the intranasal study doses (0, 500, 1000 U) of intranasal insulin at each visit. Participants will undergo a fMRI scan before and after receiving intranasal doses. Additionally, participants will have blood samples taken.; Other Names: HUMULIN R U-500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Signal response using fMRI after administration of intranasal insulin	Values of regions of interest in the fMRI will be calculated for all measures, including cerebral blood flow (CBF), at different used dosages and compared directly as well as with baseline-corrected CBF maps. The study team will determine if a significant difference at different dosages exists.	Baseline fMRI (approximately 30 minutes), fMRI Approximately 30 minutes (after insulin dose administration)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Blood Glucose (serum or point of care capillary)	Baseline (Immediately before drug administration), up to approximately 90 minutes (after drug dose)

Collaborators and Investigators

• Sponsor: Florian Schmitzberger
• Investigators: Principal Investigator: Florian Schmitzberger, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Actual): February 22, 2024
• Study Completion (Actual): February 22, 2024

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Functional Magnetic Resonance Imaging; Intranasal Insulin; Healthy Participants
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: HUM00230748

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