Effect of Glyceroltrinitrate on Human Energy Expenditure and Brown Adipose Tissue Thermogenesis
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- BAT SUVmax
研究概览
简要总结
The aim of this study is to evaluate the efficacy of glyceroltrinitrate (Nitroderm® TTS) to activate and expand human BAT as compared to mild cold exposure.
详细描述
The activation of brown adipose tissue in response to glyceroltrinitrate as compared to cold exposure will be studied in an open-label, cross-over trial in healthy volunteers with random sequence of the two study periods (treatment and control) seperated by a washout period of 7 days.
In the treatment phase all participants will receive Nitroderm® TTS (glyceroltrinitrate) for a total of 15 days. For better tolerability, it will be will started with a lower dose of 5mg/24h (Nitroderm® TTS) the first 5 days and after that a change to Nitroderm® TTS 10mg/24h for another 10 days will be done. Each transdermal patch will be applied for 12 hours per day (overnight) to avoid development of nitrate tolerance.
Energy expenditure will be measured by indirect calorimetry before and after a mild cold exposure by placing a medical cooling system around their midsection. Additionally brown adipose tissue activity will determined by 18F-FDG-PET/CT 30 min after injection of 75 MBq of 18F-FDG. To analyse changes in BAT and muscle which are caused by glyceroltrinitrate as compared with cold stimulus, a tissue biopsie of supraclavicular BAT and skeletal muscle (musculus vastus lateralis) will be performed.
To measure changes in glucose tolerance and triglyceride levels a mixed meal test will be performed during control and treatment phase respectively. Additionally, a indirect calorimetry will be conducted before and after mixed meal test to assess diet-induced thermogenesis, i.e. the increase in REE due to ingestion of nutrients
In control phase the same examinations will be performed, but without glyceroltrinitrat.
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
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI 18.5 to 25 kg/m2 or 30 to 35kg/m2
- •Able to give informed consent as documented by signature
- •Age 18 to 40 years
排除标准
- •Contraindications to glyceroltrinitrate, e.g. known hypersensitivity or allergy
- •Concomitant medication: Non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, diuretics, antihypertensives, fibrates or statins, metformin, PDE-5-inhibitors
- •Clinically significant concomitant disease states (e.g. renal failure, hepatic dysfunction, cardiovascular disease, diabetes mellitus)
- •Hypersensitivity to cold (e.g. Raynaud Syndrome)
- •Orthostatic hypotension: systolic blood pressure decreases min. 20mmHg or diastolic blood pressure decreases min 10mmHg within 3-5min after standing up (Schellong Test at screening visit)
- •History of orthostatic syncope or pre-syncope
- •Blood pressure values below 100 mmHg systolic and 60 mmHg diastolic
- •Allergy to local anesthetic
- •Hypothyroidism without sufficient substitution
- •Hyperthyroidism
- •Claustrophobia
- •Smoker / habitual tobacco use
- •Habitual excessive alcohol use
- •Weight change of >5% within 3 months prior to inclusion
- •Known or suspected non-compliance, drug or alcohol abuse
- •Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
- •Enrolment into another study using ionizing radiation within the previous 12 months
- •Pregnant or lactating women
- •Lab parameters
- •Hb below lower reference limit
- •Glycated Hemoglobin (HbA1c): above 6.0%
- •Random plasma glucose >11 mM
研究组 & 干预措施
Treatment
- administration of glyceroltrinitrate (Nitroderm TTS) for 15 days.
- measurement of energy expenditure before and after cold exposure
- performing FDG-PET/CT and tissue biopsy (brown adipose tissue and muscle)
- measurement of glucose tolerance, triglyceride levels and energy expenditure before and after a mixed meal test.
干预措施: Glyceroltrinitrat (Drug)
结局指标
主要结局
BAT SUVmax
时间窗: After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
maximum SUV in supraclavicular adipose tissue (according to BARCIST 1.0)
BAT SUVmean
时间窗: After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
18F-FDG uptake into the supra-clavicular brown adipose tissue as determined by 18F-
次要结局
- BAT Volume(After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively)
- Cold induced thermogenesis(After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively)
- Skin temperature(After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively)
- BAT glycolytic volume(After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively)
- Energy expenditure(After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively)
- Mixed meal test(After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively)