The Importance of Insulin Action in the Brain for the Immune System During Physical Activity-Overweight

The goal of this clinical trial is to clarify the interaction of central insulin action and physical activity with the immune system. Therefore, participants will undergo bicycle spiroergometer tests. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray. In another trial (NCT06552130) lean participants already have been tested. Significant effects on circulating cytokines could be identified. In this amendment, overweight persons in which brain insulin resistance is expected will be tested.

Study Overview

• Status: Not yet recruiting
• Conditions: Insulin Sensitivity
• Intervention / Treatment: Other: Spiroergometer test with intranasal placebo spray; Other: Spiroergometer test with intranasal insulin spray

Detailed Description

This research project aims to investigate if the brain insulin action regulates the immune system via the autonomous nervous system during physical activity and investigate whether participants with overweight respond different compared to lean persons. The lean persons were already studied in another trial (NCT06552130) and this trial serves as an amendment.

Insulin action in the brain will be introduced by application of insulin as nasal spray (on one day) versus carrier solution as placebo nasal spray (on another day) in a randomized, blinded fashion. Spray administration will be performed 30 minutes before a 60 min bicycle spiroergometer test at 70 % VO2max that will introduce a postprandial state. On placebo day, the known spillover of tiny amounts of nasal insulin into the systemic circulation will be mimicked by an appropriate i.v. insulin bolus. Using this approach, brain-derived regulation of the immune system including the stimulation of immune cells via cytokines, physical performance, activity of the autonomous nervous system and gene-expression of leukocytes will be examined.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin Heni, MD; Phone Number: +4973150044505; Email: martin.heni@uniklinik-ulm.de
• Study Contact Backup: Name: Sabrina Wangler; Phone Number: +4973150044782; Email: sabrina.wangler@uniklinik-ulm.de

Study Locations

• Germany
  • Ulm, Germany, 89081
    • Ulm University Hospital
    • Contact: Kathrin Popp, MD; Phone Number: +4973150044839; Email: kathrin.popp@uniklinik-ulm.de
    • Contact: Sabrina Wangler; Email: sabrina.wangler@uniklinik-ulm.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI > 28 kg/m2
• no known primary disease
• hormonal contraception with a single-phase preparation

Exclusion Criteria:

• alcohol or drug abuse
• At screening: Hb < 12 g/dl for women and Hb < 14 g/dl for men
• Any (clinical) condition that would endanger participant's safety or question scientific success according to a physician's opinion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal Insulin Spray; 160 Units of human insulin as nasal spray	Other: Spiroergometer test with intranasal insulin spray; Participants will undergo a 60 min bicycle spiroergometer test and intranasal insulin spray. Intranasal insulin will be administered 30 minutes prior to the start of the physical activity.
Placebo Comparator: Placebo Spray; Nasal spray containing placebo solution	Other: Spiroergometer test with intranasal placebo spray; Participants will undergo a 30 min bicycle spiroergometer test and intranasal placebo spray. To mimic insulin spill-over from nasal spray into systemic circulation, an i.v. insulin bolus of 3 mU × kg-1. will be administered over 15 minutes 30 minutes prior to the start of the physical activity on the placebo spray day. On the insulin spray day a comparable amount of saline will be infused.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune system activation	Influence of central nervous insulin action on the activation of the immune system activation by exercise, measured by circulating cytokines and cytokines in the supernatant of stimulated peripheral blood mononuclear cells.	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal oxygen consumption (VO2max)	Influence of central nervous insulin action on physical performance measured as VO2 peak during spiroergometry.	60 minutes
Leukocyte gene expression	Influence of central nervous insulin action on the gene expression of leukocytes during physical activity	120 minutes
Individual anaerobic threshold	Influence of central nervous insulin action on physical performance. Individual anaerobic threshold assessed by lactate measurement from venous blood sampling.	120 minutes
Catecholamines	Influence of central nervous insulin action on the activity of the autonomic nervous system recorded by means of measuring catecholamine concentrations from venous blood.	120 minutes
Heat rate variability	Influence of central nervous insulin action on the activity of the autonomic nervous system recorded by means of heart rate variability from an electrocardiogram.	120 minutes
Corticotropic pituitary axis modulation	Corticotropic pituitary axis modulation Influence of central nervous insulin action in the activity of the corticotropin pituitary axis during physical activity, measured by cortisol, dehydroepiandrosterone and adrenocorticotropic hormone	120 minutes
Effects on blood coagulation parameters	Influence of central nervous insulin action and/or physical activity on blood coagulation parameters assessed through global coagulation tests and single coagulation factors.	120 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sex differences	Potential differences in the above mentioned outcomes between sexes will be analyzed.	120 minutes
Differences between lean and overweight persons	Potential differences in the above mentioned outcomes between lean individuals studied in (NCT06552130) and overweight individuals studied in this trial.	120 minutes

Collaborators and Investigators

• Sponsor: University of Ulm
• Investigators: Principal Investigator: Martin Heni, MD, University of Ulm

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 6, 2026
• First Submitted That Met QC Criteria: March 6, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: physical activity; autonomic nervous system; immune system; brain insulin action
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Behavior; Nutritional and Metabolic Diseases; Insulin Resistance; Motor Activity
• Other Study ID Numbers: 81/24 Amendment

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