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临床试验/NCT01479075
NCT01479075已完成4 期

The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism

German Diabetes Center1 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2011年8月最近更新:
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
发起方
入组人数
30
试验地点
1
主要终点
Insulin sensitivity

研究概览

简要总结

Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism and the secretion of various hormone. The effect of intranasal insulin on peripheral metabolism in humans supposedly is mediated by the vagus nerve.

The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and whether vagus nerve stimulation can mimick this effect.

详细描述

Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism in the mouse model.

The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and energy metabolism. Intranasal insulin can be used in humans to deliver insulin to the brain and studies have shown that intranasal insulin might reduce food intake, lower body weight and modulate muscle glucose and adipose tissue lipid metabolism in himans. These effects are likely mediated by the vagus nerve as skeletal muscle insulin sensitization after intranasal insulin relates to parasympathetic tone activity (Heni et al. Diabetes 2014). Transcutaneous auricular vagus nerve stimulation (taVNS) activates non-invasively the sensory branches of the vagus nerve and is applied in humans as adjuvant treatment in drug-resistant epilepsy (Frangos et al. 2015). Thereby it can be used to examine whether the vagus nerve indeed mediates brain insulin signals to the periphery.

Here we aim to investigate the effects of intranasal insulin on hepatic glucose, lipid and energy metabolism. We further aim to test whether taVNS can mimick intranasal insulin effects on peripheral metabolism in humans.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Treatment
盲法
Single (Participant)

入排标准

年龄范围
30 Years 至 70 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Age ≥ 30 and ≤ 70 years
  • balanced gender ratio (50: 50)
  • BMI 20-25 kg/m² (normal weight subjects)
  • BMI 25-35 kg/m² (obese subjects)

排除标准

  • acute illness within the last 2 weeks before the examination
  • autoimmune diseases and disorders immune- compromised (leukocytes <5000/μl)
  • renal insufficiency (creatinine> 1.5 mg / dl)
  • heart disease, condition after heart attack
  • anemia (Hb <12 g / l, controls at each examination), blood donation within 4 weeks before the examination
  • participation in another study within 2 months before the examination
  • wear a metal or magnetic objects on or in the body
  • claustrophobia
  • use of immunomodulatory drugs (cortisol, antihistamines, aspirin)
  • thyroid disease
  • taking glitazones and insulin therapy
  • pregnancy, lactation, menstruation
  • cigarette smoking, use of alcohol or drugs, psychiatric disorders
  • risk for / or manifest AIDS (HIV) or hepatitis B or C
  • liver disease is not attributed to the existence of a non-alcoholic steatosis
  • night shift work or circumstances, which do not allow the normal day-night rhythm
  • bleeding disorders or disorders in wound healing
  • hypersensitivity to local anesthetics
  • malignant cancer
  • heart rhythm disorders
  • polyneuropathy

研究组 & 干预措施

intranasal insulin in patients

Experimental

intranasal insulin is applied to diabetic patients under fasting conditions

干预措施: intransal insulin (Drug)

intransal insulin in study participants

Experimental

intranasal insulin is applied to healthy patients under fasting conditions

干预措施: intransal insulin (Drug)

placebo in patients

Placebo Comparator

placebo spray is applied intranasally in type 2 diabetes patients under fasting conditions

干预措施: Placebo (Drug)

placebo in study participants

Experimental

placebo spray is applied intranasally in healthy participants under fasting conditions

干预措施: Placebo (Drug)

taNVS

Experimental

Transcutanoues auricular vagus nerve stimulation is applied for 14 min in the external ear in healthy participants

干预措施: taVNS (Device)

Sham stimulation

Placebo Comparator

Sham stimulation in the ear lobe is applied for 14 min in healthy participants

干预措施: sham stimulation (Device)

结局指标

主要结局

Insulin sensitivity

时间窗: 6 months

Assessment of insulin sensitivity with gold standard methods

次要结局

  • Energy metabolism(6 months)

研究者

发起方
German Diabetes Center
申办方类型
Other
责任方
Sponsor

研究点 (1)

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