Impact of Intranasal Insulin on Sympathetic Activity and Cerebral Vasodilation

Novel Treatment for Brain Insulin Resistance and Hypoperfusion

The purpose of this project is to examine the impact of increases in brain insulin on sympathetic nervous system activity, as well as peripheral and cerebral blood flow in humans.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Obesity; Insulin Resistance; Vasodilation; Autonomic Dysfunction
• Intervention / Treatment: Other: Carbon dioxide breathing; Other: Neurovascular Coupling; Drug: Human insulin

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jacqueline K Limberg, Ph.D.; Phone Number: 5738822544; Email: limbergj@missouri.edu

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65211
      • Recruiting
      • University of Missouri
      • Contact: Jacqueline K Limberg; Phone Number: 573-882-2544; Email: limbergj@missouri.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• healthy adult men and women;
• 18-45 years of age;
• BMI >18 kg/m2;
• non-pregnant/non-breastfeeding;
• non-nicotine users;

Exclusion Criteria:

• taking any medications known to affect metabolic, respiratory, cardiovascular, and/or autonomic

Self-reported history of:

• hepatic, renal, pulmonary, cardiovascular, or neurological disease;
• stroke or neurovascular disease;
• bleeding/clotting disorders;
• sleep apnea or other sleep disorders;
• diabetes;
• smoking;
• history of alcoholism or substance abuse;
• hypertension;
• respiratory disease;
• active cancer;
• autoimmune disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin (Doppler); Human insulin (160 IU) will be administered as a bolus using an intra-nasal device.	Other: Carbon dioxide breathing; Hypercapnic (5% carbon dioxide) air will be administered before and after intra-nasal insulin exposure.; Other: Neurovascular Coupling; Participants will be asked to repeatedly open and close their eyes. With eyes open, participants will focus on a visual image. This will be done before and after intra-nasal insulin exposure.; Drug: Human insulin; Participants will be administered human insulin (160 IU) as a bolus using an intra-nasal device.
Experimental: Insulin (MRI); Human insulin (160 IU) will be administered as a bolus using an intra-nasal device.	Other: Carbon dioxide breathing; Hypercapnic (5% carbon dioxide) air will be administered before and after intra-nasal insulin exposure.; Drug: Human insulin; Participants will be administered human insulin (160 IU) as a bolus using an intra-nasal device.
Other: Time Control (Doppler); Time control only	Other: Carbon dioxide breathing; Hypercapnic (5% carbon dioxide) air will be administered before and after intra-nasal insulin exposure.; Other: Neurovascular Coupling; Participants will be asked to repeatedly open and close their eyes. With eyes open, participants will focus on a visual image. This will be done before and after intra-nasal insulin exposure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of cerebral blood flow	Measured with trans-cranial Doppler ultrasound (cm/s) or arterial spin labeling (mL/100 g/min)	Change from baseline at minute 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of muscle sympathetic nerve activity (MSNA)	MSNA burst incidence (bursts/100 heart beats)	Change from baseline at minute 15
Amount of leg blood flow	Measured with Doppler ultrasound (mL/min)	Change from baseline at minute 15

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Investigators: Principal Investigator: Jacqueline K Limberg, Ph.D., University of Missouri-Columbia

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 18, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Hyperinsulinism; Insulin Resistance; Primary Dysautonomias; Autonomic Nervous System Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 2057288

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No