Quantifying Brown Adipose Tissue Thermogenesis in Type 2 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- BAT volume
研究概览
简要总结
Activation of brown adipose tissue (BAT) by cold exposure.
BAT thermogenesis and BAT volume of metabolic activity will be assessed by Positron-Emitting-Tomography (PET/CT) and MRI/MRS imaging and new pharmacological methods to modulate BAT thermogenesis.
All previous data on the functioning of Brown Adipose Tissue (BAT) were obtained by Positron-Emitting-Tomography (PET) imaging studies using fluorodeoxyglucose F18 ( [18F]- FDG). This approach underestimates the actual activity of the BAT. In this study, the investigator is going to use a new PET tracer (C11-palmitate) which is a fat molecule. This will allow to quantify more accurately the activity of brown fat.
详细描述
The study protocol includes three visits: the screening visit (V1) and two PET/MRI imaging studies (V2 and V3) performed in random order at an interval of 7 to 14 days.
PET/ MRI studies will be performed with and without nicotinic acid. A total of 500 mg of nicotinic acid will be given orally, at a rate of 2 doses of 150 mg and 2 doses of 100 mg, through V2 (protocol A): one dose at time 0, 60 minutes, 120 minutes and 180 minutes.
During V2 and V3, participants will undergo Acute Cold Exposure to stimulate brown adipose tissue.
The morning of each PET imaging study, the participants will follow an MRI acquisition to determine hepatic, pancreatic, visceral and BAT lipid content, followed by an MRS acquisition in the hepatic and cervico-thoracic region. MRI and MRS acquisition of the hepatic and cervico-thoracic region will be repeated again at the end of the day.
The radioactive PET tracers used in this study are the [11C]-acetate, [11C]-palmitate and [18F]-FDG followed by dynamic and whole-body scans.
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
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •10 men and 10 women with T2D.
- •10 non-diabetic men and 10 non-diabetic women (matched for sex, BMI and age to the T2D participants).
排除标准
- •Change in weight of more than 2 kg over the past 3 months or recent changes in lifestyle;
- •Treatment with a fibrate, thiazolidinedione, insulin, beta-blocker, GLP-1 agonist, or other drug known to affect lipid or carbohydrate metabolism, except statins, metformin, sulfonylurea, DPP-IV inhibitor and other antihypertensive agents that can be temporarily stopped safely prior to the studies, as per our approved protocols;
- •Presence of overt cardiovascular, liver, renal or other medical conditions;
- •Smoking or consumption of more than 2 alcoholic beverages per day;
- •Any other contraindication to temporarily suspending current medications for lipids or hypertension;
- •Any contraindication to MRI scanning.
- •Having participated to a research study with exposure to radiation in the last two years before the start of the study.
研究组 & 干预措施
Subject with Type 2 Diabetes- cold exposure
3-hour cold exposure: Protocol B
干预措施: Cold exposure (Other)
Subject with type 2 Diabetes- cold exposure and nicotinic acid
3-hour cold exposure with oral nicotinic acid: Protocol A
干预措施: Cold exposure (Other)
Subject with type 2 Diabetes- cold exposure and nicotinic acid
3-hour cold exposure with oral nicotinic acid: Protocol A
干预措施: Oral Nicotinic acid (Drug)
Subject without Type 2 Diabetes- cold exposure
3-hour cold exposure: Protocol B
干预措施: Cold exposure (Other)
Subject without type 2 Diabetes- cold exposure and nicotinic acid
3-hour cold exposure with oral nicotinic acid: Protocol A
干预措施: Cold exposure (Other)
Subject without type 2 Diabetes- cold exposure and nicotinic acid
3-hour cold exposure with oral nicotinic acid: Protocol A
干预措施: Oral Nicotinic acid (Drug)
结局指标
主要结局
BAT volume
时间窗: 180 minutes after the start of the cold exposure
Assessed using i.v. injection of 18FDG with whole-body PET/CT acquisition.
Brown Adipose Tissue (BAT) Glucose uptake
时间窗: 150 minutes after the start of the cold exposure
Assessed using i.v. injection of 18FDG with sequential dynamic PET/CT scanning
次要结局
- BAT triglyceride content(at baseline and at time 180 (for CT) and 240 (for MR) after cold exposure.)
- Hepatic Glucose production(-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.)
- Substrate utilisation(-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.)
- Activation of BAT (oxidative metabolism)(90 minutes after beginning cold exposure)
- Fatty Acid uptake and metabolism(at baseline and at time 120 minutes after beginning cold exposure)
- Whole-body lipolysis(-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.)
- Changes in insulin level and secretion(-150 and 0 minutes before and 60, 120 and 180 minutes after cold exposure.)
研究者
André Carpentier
tenured professor
Université de Sherbrooke