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

NCT ID: NCT06912048

Last Updated: 2025-07-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-14
• Study Completion Date: 2027-05-31

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.

Detailed Description

This research project aims to investigate to what extent the parasympathetic nervous system is responsible for the transmission of signals from the brain to peripheral organs. Furthermore, the study will investigate sex differences and differences between healthy and high-risk individuals on brain-derived coordination of postprandial signaling for metabolic control.

Therefore, parasympathetic blockade will be introduced by atropine infusion (on one day) versus saline infusion as placebo (on another day) in a randomized fashion. For safety reasons, only the participants will be blinded. Infusion will start 20 minutes before a 75 gram oral glucose tolerance test (oGTT) and last until the end of the 2h oGTT. The oGTT will introduce a postprandial state. Additionally, 1000 mg Paracetamol will be added to the solution to study gastric emptying.

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 (120 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).

Conditions

Autonomic Function

Study Design

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

Study Groups

Atropine Infusion

5 µg x kg fat free mass-1 x h-1

Group Type: EXPERIMENTAL

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

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. 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.

Saline infusion

Group Type: PLACEBO_COMPARATOR

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

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. 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.

Interventions

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

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.

Intervention Type: OTHER

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

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.
• Liver dysfunction
• Renal insufficiency

• Minimum Eligible Age: 18 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

Ulm University Hopital

Locations

Ulm University Hospital

Ulm, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Martin Heni, MD

Role: CONTACT

martin.heni@uniklinik-ulm.de

+4973150044505

Andrea Geissler

Role: CONTACT

andrea.geissler@uniklinik-ulm.de

Facility Contacts

Sabrina Wangler

Role: primary

sabrina.wangler@uniklinik-ulm.de

+4973150044782

Andrea Geissler

Role: backup

andrea.geissler@uniklinik-ulm.de

Other Identifiers

101125605

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

467/2024

Identifier Type: -

Identifier Source: org_study_id