The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS a Randomized, Controlled, Double Blinded Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Changes in total lipid content in the liver
研究概览
简要总结
Non-alcoholic fatty liver disease (NAFLD) is a common human liver pathology, closely associated with the obesity pandemic and insulin resistance. In the insulin resistant state the liver remains sensitive to pro-lipogenic signals of insulin, which further promote lipid accumulation. Secretion of very-low-density-lipoproteins (VLDL), the main carriers of triglycerides (TG) in the plasma, is the principal pathway for the liver to mobilize and dispose of lipids. Thus, hepatic TG export must not be too low in order to prevent steatosis. Our preliminary data from animal experiments suggest that enhanced brain insulin signaling promotes hepatic VLDL secretion, and reduces lipid accumulation in the liver. It remains to be tested whether other insulin sensitive tissues, such as the myocardium or the skeletal muscle, are also affected. In humans, neuropeptides, including insulin, can be delivered to the brain via an intranasal (IN) route of administration, without causing relevant systemic side effects.
Therefore, we hypothesize that by enhancing brain insulin signaling using chronic IN insulin administration hepatic TG export increases and prohibits lipid accumulation in the liver and other insulin sensitive tissues, such as the myocardium and the skeletal muscle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •BMI 22 - 27 kg/m2
- •Age between 18 - 65 years
排除标准
- •regular medication
- •metabolic or liver illnesses
- •tendency towards claustrophobia
- •Chronic sinusitis, diagnosed nasal polyposis, diagnosed severe septum deviation
- •metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation [heart pacemaker, brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, post coronary by-pass graft (epicardial pace wires), penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body].
研究组 & 干预措施
Insulin dilution buffer
During a subsequent 4-week treatment phase subjects will be randomly assigned to receive intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed. 40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia.
Ectopic lipid content and heart function will be assessed weekly by non-invasive 1H magnetic resonance spectroscopy.
干预措施: Insulin Dilution Buffer (Novo Nordisk) (Drug)
Insulin dilution buffer
During a subsequent 4-week treatment phase subjects will be randomly assigned to receive intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed. 40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia.
Ectopic lipid content and heart function will be assessed weekly by non-invasive 1H magnetic resonance spectroscopy.
干预措施: 1H magnetic resonance spectroscopy (Other)
Intranasal Insulin administration
During a subsequent 4-week treatment phase subjects will be randomly assigned to receive intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed. 40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia.
Ectopic lipid content and heart function will be assessed weekly by non-invasive 1H magnetic resonance spectroscopy.
干预措施: Intranasal insulin administration (Drug)
Intranasal Insulin administration
During a subsequent 4-week treatment phase subjects will be randomly assigned to receive intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed. 40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia.
Ectopic lipid content and heart function will be assessed weekly by non-invasive 1H magnetic resonance spectroscopy.
干预措施: 1H magnetic resonance spectroscopy (Other)
结局指标
主要结局
Changes in total lipid content in the liver
时间窗: one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
1H magnetic resonance spectroscopy
次要结局
- Changes of myocardial lipid content(baseline, 2 and 4 weeks after intranasal insulin administration)
- Changes of skeletal muscle lipid content(baseline, 2 and 4 weeks after intranasal insulin administration)
- Changes of hepatic Lipid composition(one week before & baseline & 1,2,3 and 4 weeks after intranasal insulin administration)
- Changes of myocardial lipid composition(baseline, 2 and 4 weeks after intranasal insulin administration)
- Changes of lipid composition in skeletal muscle(baseline, 2 and 4 weeks after intranasal insulin administration)
- changes in heart function(baseline, 2 and 4 weeks after intranasal insulin administration)
研究者
Prof. Dr. Michael Krebs
Prof. MD
Medical University of Vienna