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

University of Ulm

Status

Enrolling

Conditions

Autonomic Function

Treatments

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

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

Study type

Interventional

Funder types

Other

Identifiers

NCT06912048

467/2024

101125605 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment

52 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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