Relative Contribution of Brain Insulin Action for Postprandial Metabolism

NCT06295640 | Active Not Recruiting

• 1 other identifier: 300/2022
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to clarify (i) the contribution of brain insulin action on regulation of systemic metabolism, (ii) sex-specific differences in the central regulation and (iii) the influence of the menstrual cycle in women. Therefore, participants will undergo oral glucose tolerance tests combined with a double tracer dilution technique. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray.

Conditions

Glucose Metabolism Disorders

Keywords

postprandial glucose metabolism; brain insulin action; insulin sensitivity; insulin secretion; endogenous glucose production; menstrual cycle; sex differences; proglucagon cleavage products

Outcome Measures

Primary Outcomes (2)

• Endogenous glucose production

  Effect of intranasal insulin versus placebo on endogenous glucose production assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.

  -120 minutes - 180 minutes during oral glucose tolerance test

• Rate of glucose disappearance

  Effect of intranasal insulin versus placebo on rate of glucose disappearance (Rd) assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.

  -120 minutes - 180 minutes during oral glucose tolerance test

Secondary Outcomes (8)

• Proglucagon cleavage products

  0-120 minutes during oral glucose tolerance test

• Glucose tolerance

  0-120 minutes during oral glucose tolerance test

• Whole-body insulin sensitivity

  0-120 minutes during oral glucose tolerance test

• Insulin secretion

  0-180 minutes during oral glucose tolerance test

• Post-absorptive energy expenditure

  30 minutes and 180 minutes during oral glucose tolerance test

Study Arms (2)

Intranasal insulin spray

EXPERIMENTAL

160 Units of human insulin as nasal spray

Other: Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray

Placebo spray

PLACEBO COMPARATOR

Nasal spray containing placebo solution

Other: Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray

Interventions

Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray OTHER

Subjects will undergo a 75 g OGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. \[6,6-2H\]glucose will be infused for a total of 300 minutes,while the infusion will start 120 minutes prior the OGTT and will last until the end of the OGTT. Placebo spray will be administered 15 minutes prior to the start of the OGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with \[U-13C6\]-glucose. 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 ten minutes starting at time point -15 minutes on the placebo spray day. On the insulin spray day a comparable amount of saline will be infused.

Placebo spray

Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray OTHER

Subjects will undergo a 75 g OGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. \[6,6-2H\]glucose will be infused for a total of 300 minutes,while the infusion will start 120 minutes prior the OGTT and will last until the end of the OGTT. Intranasal insulin will be administered 15 minutes prior to the start of the OGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with \[U-13C6\]-glucose.

Intranasal insulin spray

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI \< 24 kg/m2
• no known primary diseases
• no hormonal contraception

You may not qualify if:

• Alcohol or drug abuse
• Smoking
• 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.

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (1)

Universityhospital Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Glucose Metabolism Disorders; Insulin Resistance

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Martin Heni, MD

  University of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. Martin Heni

Model Details: Randomized, controlled, cross-over design for men. Randomized, controlled, 2x2 factorial cross-over design for women taking the menstrual cycle phase into account.

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: March 6, 2024
• Study Start: March 18, 2024
• Primary Completion: September 5, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 17, 2026

Record last verified: 2025-11

Locations

DE (1)