Understanding Individual Variability in Neuronal Signal Transmission to Target Organs in Health and Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Glucose tolerance
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •Drug and/or alcohol abuse
- •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
研究组 & 干预措施
Atropine Infusion
5 µg x kg fat free mass-1 x h-1
干预措施: Oral glucose tolerance test with double-tracer dilution and atropine infusion (Other)
Saline infusion
干预措施: Oral glucose tolerance test with double-tracer dilution and saline infusion (placebo) (Other)
结局指标
主要结局
Glucose tolerance
时间窗: 120 minutes
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.
Insulin Sensitivity
时间窗: 120 minutes
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.
Insulin Secretion
时间窗: 180 minutes
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.
次要结局
- Lipolysis(120 minutes)
- Gastric emptying(120 minutes)
- Amino Acid Metabolism(120 minutes)
- Bile acid metabolism(120 minutes)
- Substrate oxidation(230 Minutes)
- Incretin secretion(120 minutes)
- Sex differences(180 minutes)
- Autonomic nervous system(180 minutes)
- Sex differences(180 minutes)
- Lipolysis(120 minutes)
- Gastric emptying(120 minutes)
- Amino Acid Metabolism(120 minutes)
- Blood coagulation parameters(120 Minutes)
- Bile acid metabolism(120 minutes)
- Substrate oxidation(230 Minutes)
- Incretin secretion(120 minutes)
- Autonomic nervous system(180 minutes)
研究者
Martin Heni
Prof. Dr. med. Martin Heni
University of Ulm