The Effect of Weekly Semaglutide Treatment on Energy Expenditure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Changes of Energy Expenditure Assessed by Chamber
研究概览
简要总结
This study will test the effects of weekly injections of the glucagon like peptide-1 (GLP-1) agonist semaglutide on energy expenditure and metabolic parameters in a 24 week double-blind, placebo-controlled dose escalation randomized trial. After baseline testing, 52 patients will be randomly assigned to the semaglutide or matching placebo injection group. In addition to taking medication or placebo, all participants will a calorie restricted diet provided by the researchers, providing 600 kcals per day below their estimated baseline requirements. Before and at the end of treatment, weight status, body composition, basal metabolic rate (BEE), 24h energy expenditure, daily total energy expenditure (TEE) for free living, physical activity, energy intake (questionnaire and food table), and hormone parameters for energy homeostasis will be evaluated.
详细描述
Obesity is a complex chronic recurrent multifactorial disease characterized by abnormal or excessive body fat, which impairs physical health. In recent years, the glucagon like peptide-1 (GLP-1) receptor agonist semaglutide has attracted much attention due to its significant impact on weight loss. It can not only effectively control blood sugar by regulating the secretion of insulin and glucagon. It can also participate in certain brain regions of the body at pharmacological doses, regulating food intake and consumption. Semaglutide reduces energy intake and achieves weight loss by delaying gastric emptying, suppressing appetite, reducing hunger, and increasing satiety. This effect has been proven to be produced by activating the glucagon like peptide-1 (GLP-1) receptors in the central nervous system, further indirectly regulating the activity of neurons involved in appetite regulation, food intake, and preference.
The previous results of using GLP-1 receptor agonist (RA) in rats and humans provide promising evidence data to support current randomized clinical trials. Peripheral administration of GLP-1 or GLP-1 RA can reduce blood sugar and energy intake in humans and rodents, and long-term treatment can lead to weight loss. In mice the drug also sustains energy expenditure at levels similar to controls, preventing the reduction that normally accompanies caloric restriction. Whether the same effects occur in humans is unclear because no studies have yet been performed comparing semaglutide treated individuals with those on a standard calorie restricted diet (in effect pair feeding). Therefore, in this study, researchers will use doubly- labelled water (DLW) and respiratory chambers to investigate whether semaglutide can prevent the reduction of energy expenditure that typically occurs during energy restriction.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age 18-60 years at time of enrollment
- •BMI ≥ 25 kg/m²
排除标准
- •Weight change exceeding 5 kilograms (11 pounds) in the past 90 days
- •Surgical treatment for past obesity, dieting, or undergoing weight loss treatment
- •Irregular diet and lifestyle, unhealthy habits such as smoking, alcohol, and drugs
- •Patients with metabolic diseases, basic diseases or infectious diseases
- •Patients with a personal or family history of medullary thyroid carcinoma (MTC), or patients with rare type 2 multiple endocrine tumor syndrome (MEN 2)
- •Current use of any other GLP1 receptor agonist
- •Pregnancy, lactation or expectation to conceive during study period (8) Subject with contraindication to neuroimaging by MRI (9) People with fear of blood and pathologically low blood pressure (10) Use of antibiotics and probiotics within 8 weeks
- •11) Subject unlikely to adhere to study procedures in opinion of investigator
研究组 & 干预措施
Semaglutide
Once-weekly injections of gradually increased doses of semaglutide
干预措施: Semaglutide (Drug)
Placebo
Once-weekly injections of gradually increased volumes of saline placebo, to match the volumes of the semaglutide treated arm.
干预措施: Placebo (Drug)
结局指标
主要结局
Changes of Energy Expenditure Assessed by Chamber
时间窗: From baseline at week 0 to week 24
The total energy expenditure in a free living environment is measured using a 24-hour chamber.
Changes of Physical Activity
时间窗: From baseline at week 0 to week 24
Physical activity of the participants will be recorded using GT3X accelerometer worn near the hip for a consecutive period of 14 days. The monitor should not be worn while bathing or swimming. The first day is discarded along with any day where the wear time is less than 12 hours. For a valid measure the goal is to get 2 weekday and 2 weekend days.
Changes of Total Energy Expenditure Assessed by Doubly Labeled Water Analysis
时间窗: From baseline at week 0 to week 24
TEE will be measured using the DLW method. Urine samples from all participants in the DLW subset will be stored at -20 ℃ and shipped on dry ice for analysis in the laboratory of Dr. John Speakman at the Shenzhen Institute of Advanced Technology, Chinese academy of sciences. Isotopes will be measured in benchtop near-infrared isotope gas analyzer, and mean CO2 production will be calculated from isotope ratios using the recently derived equation (Speakman et al 2021: Cell reports medicine). TEE will then be calculated using mean CO2 production using the Weir equation.
Changes of Resting Energy Expenditure
时间窗: From baseline at week 0 to week 24
Resting energy expenditure will be measured using indirect calorimetry via a respiratory hood system (Cosmed). The subject attends in the lab after an overnight fast. The person lies down on a flat bed and the hood is placed over their head. Metabolic rate (oxygen consumption and CO2 production) are monitored for 40 minutes. The last 10 minutes is used as the measurement. Calorimeters will be assessed with a turbine test to ensure accuracy of measurements. Validation via an alcohol burn will be performed monthly.
次要结局
- Body Mass Index (BMI)(From baseline at week 0 to week 24)
- Waist and Hip circumferences(From baseline at week 0 to week 24)
- Fat mass(From baseline at week 0 to week 24)
- Changes in Body Composition as Assessed by Body Fat Mass Using Dual Energy X-ray Absorptiometry (DEXA)(From baseline at week 0 to week 24)
- Change in SF-36: role-physical score(From baseline at week 0 to week 24)
- Subjects who achieve responder definition value for SF-36 physical functioning score (yes/no)(From baseline at week 0 to week 24)
- Change in HbA1c(From baseline at week 0 to week 24)
- Body Weight(From baseline at week 0 to week 24)
- Body shape(From baseline at week 0 to week 24)
- Changes in Fat and Total Calorie Intake Assessed by Free Buffet Meal Analysis(From baseline at week 0 to week 24)
- Energy intake during ad libitum lunch(From baseline at week 0 to week 24)
- Body water(From baseline at week 0 to week 24)
- Mean postprandial rating - Hunger(From baseline at week 0 to week 24)
- Change in lipids: Total cholesterol(From baseline at week 0 to week 24)
- Change in lipids: Low density lipoprotein (LDL) cholesterol(From baseline at week 0 to week 24)
- Change in lipids: Very low density lipoprotein (VLDL) cholesterol(From baseline at week 0 to week 24)
- Organ sizes(From baseline at week 0 to week 24)
- Body temperature from surface temperature of the forehead(From baseline at week 0 to week 24)
- Overall appetite score (OAS) before and after intake of a standardised meal(From baseline at week 0 to week 24)
- Change in SF-36: vitality score(From baseline at week 0 to week 24)
- Change in SF-36: physical component summary(From baseline at week 0 to week 24)
- Number of treatment emergent adverse events (TEAEs)(From baseline at week 0 to week 24)
- Change in amylase(From baseline at week 0 to week 24)
- Change in lipase(From baseline at week 0 to week 24)
- Metabolites in serum, feces and urine(From baseline at week 0 to week 24)
- Far free mass(From baseline at week 0 to week 24)
- Change in energy intake of test meal(From baseline at week 0 to week 24)
- Mean postprandial rating - Fullness(From baseline at week 0 to week 24)
- Mean postprandial rating - Satiety(From baseline at week 0 to week 24)
- Change in SF-36: bodily pain score(From baseline at week 0 to week 24)
- Microbiome(From baseline at week 0 to week 24)
- Bone mass(From baseline at week 0 to week 24)
- Change in physical functioning score(From baseline at week 0 to week 24)
- Change in SF-36: general health score(From baseline at week 0 to week 24)
- Change in SF-36: mental health score(From baseline at week 0 to week 24)
- Change in systolic and diastolic blood pressure(From baseline at week 0 to week 24)
- Blood glucose(From baseline at week 0 to week 24)
- Change in fasting serum insulin(From baseline at week 0 to week 24)
- Change in lipids: High density lipoprotein (HDL) cholesterol(From baseline at week 0 to week 24)
- Change in lipids: Free fatty acids (FFA)(From baseline at week 0 to week 24)
- Genetics(From baseline at week 0 to week 24)
- Number of serious adverse events (SAEs)(From baseline at week 0 to week 24)
- Changes of Circulating Leptin Levels(From baseline at week 0 to week 24)
- Mean postprandial rating - Prospective food consumption(From baseline at week 0 to week 24)
- Change in SF-36: social functioning score(From baseline at week 0 to week 24)
- Change in SF-36: role-emotional score(From baseline at week 0 to week 24)
- Change in SF-36: mental component summary(From baseline at week 0 to week 24)
- Change in lipids: Triglycerides(From baseline at week 0 to week 24)
- Change in fatty liver index (FLI) score category(From baseline at week 0 to week 24)
- Subjects who have permanently discontinued randomised trial product (yes/no)(From baseline at week 0 to week 24)
- Time to permanent discontinuation of randomised trial product(From baseline at week 0 to week 24)
- Changes in Inflammation Assessed by C-reactive Protein (CRP)(From baseline at week 0 to week 24)
- Change in pulse(From baseline at week 0 to week 24)
- Circulating hormones(From baseline at week 0 to week 24)
研究者
John R. Speakman
Professor, Chief Scientist
Shenzhen Institutes of Advanced Technology ,Chinese Academy of Sciences