Short Term Effect of Fluvastatin on Brown Adipose Tissue Thermogenesis and Activity in Humans
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- (18)F-FDG uptake in the supraclavicular brown adipose tissue measured by PET by the maximum standardized uptake value (SUVmax)
研究概览
简要总结
The purpose of this study is to elucidate the effects of Fluvastatin on brown adipose tissue activity in humans.
详细描述
Statins, inhibitors of cholesterol biosynthesis, act by inhibiting the enzyme of the mevalonate pathway. Although the clinical benefits of statins are undisputable, they have been shown to increase insulin resistance and incidence of type 2 diabetes mellitus, the mechanism of which is currently not clear.
The main function of brown adipose tissue (BAT) is non-shivering thermogenesis (i.e. heat production through energy dissipation) in brown adipocytes. There has been a growing interest in BAT as a novel therapeutic approach to increase energy expenditure in order to facilitate weight-loss and increase insulin sensitivity.
BAT activity will be assessed using calorimetric test and [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET).
We speculate that statins inhibit BAT function and that this mechanism may contribute to the above mentioned increase in insulin resistance.
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 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
- Male
- 接受健康志愿者
- 是
入选标准
- •Male volunteers (18-40 y)
- •body mass index 19 to 27 kg/m²
- •Fluent in German or English
排除标准
- •Regular physical exercise of more than >150 min of exercise per week.
- •Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
- •Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.),
- •Clinically indicated intake of the following medications: Corticosteroids, CYP3A4-Inhibitors (Itraconazol, Voriconazol, Fluconazol, Clarithromycin, Erythromycin, Indinavir, Nelfinavir, Ritonavir, Grapefruit juice), Beta-Blocker, Neuroleptics, Tricyclic Antidepressants,
- •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,
- •Participation in another study with investigational drug within the 30 days preceding and during the present study,
- •Participation in another study involving ionizing radiation in the same year,
- •Previous enrolment into the current study,
- •Enrolment of the investigator, his/her family members, employees and other dependent persons,
- •MRI contraindications: Not MRI-compatible metal in the body, cardiac pacemaker, History of surgery with possible metal clips/parts still in the body, claustrophobia.
- •Resting pulse rate > 70 bpm
- •Known arterial hypertension or resting blood pressure > 130/80 mmHg.
- •frequence corrected QT-time (QTc) >430 ms
- •Serum creatinine > 1.5x upper limit of norm (ULN), i.e.> 145 µmol/L
- •creatine kinase > 1.5x ULN, i.e. > 300 U/L
- •aspartate transaminase (ASAT) > 1.5x ULN, i.e. > 51 U/L
- •alanine aminotransferase (ALAT) > 1.5x ULN, i.e. > 88 U/L
- •Hypothyroidism
- •Vitamin D deficiency, Vitamin D3 < 25 nmol/L
- •Intake of anticoagulants or inhibitors of platelet aggregation (e.g. Aspirin, clopidogrel).
- •Known tendency to form keloids (hypertrophic scar tissue)
研究组 & 干预措施
Experimental
Volunteers receive calorimetric tests and FDG PET scans pre and post 2 weeks of Fluvastatine.
干预措施: Fluvastatin (Drug)
结局指标
主要结局
(18)F-FDG uptake in the supraclavicular brown adipose tissue measured by PET by the maximum standardized uptake value (SUVmax)
时间窗: 14 days
Cold and Mirabegron induced 18F-FDG uptake into the supra-clavicular brown adipose tissue (scBAT) as determined by 18F-FDG PET/MR standardized uptake value (SUVmax) after two weeks of treatment with Fluvastatin.
次要结局
- The mean standardized uptake value for 18F-FDG uptake (SUVmean) in the supraclavicular adipose tissue depot(14 days)
- fat fraction with T2 relaxation time of the BAT depot(14 days)
- Volume of supraclavicular BAT(14 days)
- Cold induced thermogenesis(14 days)
- Supraclavicular skin temperature in response to mild cold stimulus(14 days)