Understanding Individual Variability in Neuronal Signal Transmission to Target Organs in Health and Disease

NCT06912048 | Recruiting

• 2 other identifiers: 467/2024101125605
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the influence of parasympathetic transmission from the brain to different metabolic organs. This transmission can be blocked with the muscarinic antagonist atropine. Participants will undergo an oral glucose tolerance test combined with a double tracer dilution technique either with atropine infusion or placebo. Healthy individuals and high-risk individuals will be compared to identify possible changes in signaling in high-risk groups. In addition, men and women will be included to take into account possible sex differences.

Conditions

Autonomic Function

Keywords

parasympathetic transmission; autonomic nervous system; brain periphery crosstalk; metabolism; insulin sensitivity; insulin secretion; endogenous glucose production; sex differences; high risk population

Outcome Measures

Primary Outcomes (3)

• Glucose tolerance

  Effect of parasympathetic blockade with atropine versus placebo on glucose tolerance assessed as area under the glucose curve (0-120 minutes) and glucose levels at timepoint 120 minutes during the 75 g oral glucose tolerance test.

  120 minutes

• Insulin Sensitivity

  Effect of parasympathetic blockade with atropine versus placebo on insulin sensitivity assessed from glucose and insulin measurements during the 75 g oral glucose tolerance test.

  120 minutes

• Insulin Secretion

  Effect of parasympathetic blockade with atropine versus placebo on insulin secretion assessed from glucose and insulin/C-peptide measurements during the 75 g oral glucose tolerance test.

  180 minutes

Secondary Outcomes (9)

• Lipolysis

  120 minutes

• Gastric emptying

  120 minutes

• Amino Acid Metabolism

  120 minutes

• Bile acid metabolism

  120 minutes

• Substrate oxidation

  230 Minutes

Other Outcomes (6)

• Circulating peptides

  120 minutes

• Lipids and lipoproteins

  120 minutes

• Metabolites

  120 minutes

Study Arms (2)

Atropine Infusion

EXPERIMENTAL

5 µg x kg fat free mass-1 x h-1

Other: Oral glucose tolerance test with double-tracer dilution and atropine infusion

Saline infusion

PLACEBO COMPARATOR

Other: Oral glucose tolerance test with double-tracer dilution and saline infusion (placebo)

Interventions

Oral glucose tolerance test with double-tracer dilution and atropine infusion 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. Atropine infusion will be administered 20 minutes before the start of the oGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with \[U-13C6\]-glucose.

Atropine Infusion

Oral glucose tolerance test with double-tracer dilution and saline infusion (placebo) 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. Saline infusion will be administered 20 minutes before the start of the oGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with \[U-13C6\]-glucose.

Saline infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: at least 18
• BMI: 20 - 24.9 kg/m2 (for the healthy groups) or more than 28 kg/m2 (for the overweight groups)
• For women: Hormonal contraception with a single-phase preparation (e.g. Nuvaring)
• Understanding and voluntarily signing an informed consent form prior to study-related examinations

You may not qualify if:

• Drug and/or alcohol abuse
• smoking
• Taking medication that affects blood sugar or addresses the central and/or autonomic nervous system (e.g. anti-epileptic drugs, beta blockers, dopamine agonists, antidepressants). Taking antihistamines.
• Pre-existing cardiac conditions
• Neurological pre-existing conditions
• Known cardiac arrhythmia
• Known allergies to ingredients, e.g. paracetamol and atropine
• Known narrow-angle glaucoma
• Known hyperthyroidism
• Known diseases of the urinary tract or prostate
• Pregnancy or breastfeeding
• At screening: Hb \< 12 g/dl for women and Hb \< 14 g/dl for men
• No consent to be informed about incidentally discovered pathological findings
• Any (clinical) condition which, in the opinion of the physician, could jeopardize the safety of the
• or would jeopardize the scientific success.

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (1)

Ulm University Hospital

Ulm, 89081, Germany

RECRUITING

MeSH Terms

Conditions

Insulin Resistance

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

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

  Ulm University Hopital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Heni, MD

CONTACT

+4973150044505; martin.heni@uniklinik-ulm.de

Andrea Geissler

CONTACT

andrea.geissler@uniklinik-ulm.de

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

Study Record Dates

• First Submitted: March 28, 2025
• First Posted: April 4, 2025
• Study Start: May 14, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)