Relative Contribution of Brain Insulin Action for Postprandial Metabolism

NCT ID: NCT06295640

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-18
• Study Completion Date: 2026-01-31

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.

Detailed Description

This research project aims to investigate to what extent brain insulin action is responsible for the control of postprandial metabolism compared to direct effects of insulin in peripheral target tissues. Furthermore, the study will investigate sex differences and the influence of the menstrual cycle on brain-derived coordination of postprandial signaling for metabolic control.

Therefore, 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 15 minutes before a 75 gram oral glucose tolerance test 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. This approach will be combined with a double-tracer dilution technique. Labeled glucose ([6,6-2H]glucose) will be infused 120 minutes before and during the OGTT (180 min) and will be used to address endogenous glucose production. The glucose drink from the OGTT will be enriched with [U-13C6]glucose to compute the glucose appearance rate (Ra). Basal endogenous glucose production will be calculated as well as post-load endogenous glucose production and rates of glucose disappearances (Rd). Using this approach, brain-derived regulation of postprandial metabolism including endogenous glucose production, glucose disappearance, insulin secretion, and secretion of proglucagon-cleavage products (incretins) will be examined.

Conditions

Glucose Metabolism Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Intranasal insulin spray

160 Units of human insulin as nasal spray

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Placebo spray

Nasal spray containing placebo solution

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: 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.

Interventions

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

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.

Intervention Type: OTHER

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

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Ulm

OTHER

Sponsor Role: lead

Responsible Party

Martin Heni

Prof. Dr. med. Martin Heni

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martin Heni, MD

Role: PRINCIPAL_INVESTIGATOR

University of Ulm

Locations

Universityhospital Ulm

Ulm, , Germany

Countries

Germany

Other Identifiers

300/2022

Identifier Type: -

Identifier Source: org_study_id