The Effect of Weekly Semaglutide Treatment on Energy Expenditure

Obesity; Drug Clinical Trial

Official title:

The Effect of Weekly Semaglutide Treatment on Energy Expenditure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06390501
• Other study ID #: SIAT-IRB-231215-H0705
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: September 15, 2025

Study information

• Verified date: April 2024
• Source: Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
• Contact: John R Speakman, phD
• Phone: 13466654659
• Email: j.speakman[@]abdn.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 15, 2025
• Est. primary completion date: August 15, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

Inclusion criteria:

1. Age 18-60 years at time of enrollment

2. BMI = 25 kg/m²

Exclusion criteria:

1. Weight change exceeding 5 kilograms (11 pounds) in the past 90 days

2. Surgical treatment for past obesity, dieting, or undergoing weight loss treatment

3. Irregular diet and lifestyle, unhealthy habits such as smoking, alcohol, and drugs

4. Patients with metabolic diseases, basic diseases or infectious diseases

5. Patients with a personal or family history of medullary thyroid carcinoma (MTC), or patients with rare type 2 multiple endocrine tumor syndrome (MEN 2)

6. Current use of any other GLP1 receptor agonist

7. 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

Related Conditions & MeSH terms

• Obesity; Drug

Intervention

Drug:
• Semaglutide
Solution for subcutaneous (s.c. - under the skin) injection. 0.25 mg semaglutide once weekly for four weeks, 0.5 mg semaglutide once weekly for four weeks, 0.1 mg semaglutide once weekly for four weeks, 1.7 mg semaglutide once weekly for four weeks followed by 2.4 mg semaglutide once weekly for eight weeks
• Placebo
Solution for subcutaneous (s.c. - under the skin) injection

Locations

Country	Name	City	State
China	Shenzhen Institute of Advanced Technology	Shenzhen

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of Total Energy Expenditure Assessed by Doubly Labeled Water Analysis	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.	From baseline at week 0 to week 24
Primary	Changes of Energy Expenditure Assessed by Chamber	The total energy expenditure in a free living environment is measured using a 24-hour chamber.	From baseline at week 0 to week 24
Primary	Changes of Resting Energy Expenditure	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.	From baseline at week 0 to week 24
Primary	Changes of Physical Activity	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.	From baseline at week 0 to week 24
Secondary	Body Weight	Subjects will be asked to fast overnight and weight will be measured using a calibrated Seca body weight scale first thing in the morning on subjects wearing light clothes and no shoes.	From baseline at week 0 to week 24
Secondary	Body Mass Index (BMI)	Percent change of body mass index (BMI), as calculated by the formula: body weight in kg divided by height in meters², between baseline and the end of the 24-week randomized drug treatment phase.	From baseline at week 0 to week 24
Secondary	Waist and Hip circumferences	Waist and Hip circumferences will be measured using a whole body laser scanner.	From baseline at week 0 to week 24
Secondary	Body shape	Body shape will be measured using a whole body laser scanner.	From baseline at week 0 to week 24
Secondary	Fat mass	Fat mass will be measured by Magnetic Resonance Imaging (Shanghai united imaging, uMR 790 ).	From baseline at week 0 to week 24
Secondary	Far free mass	Fat free mass will be measured by Bioimpedance Analysis (Tanita, MC-980).	From baseline at week 0 to week 24
Secondary	Organ sizes	Volumes of the brain, liver, spleen, pancreas, kidneys, subcutaneous and visceral adipose tissue, skeletal muscle in the limbs, trunk and shoulders will be measured by Magnetic Resonance Imaging (Shanghai united imaging, uMR 790 ).	From baseline at week 0 to week 24
Secondary	Bone mass	Bone mass will be measured by Dual Energy X-ray Absorptiometry (DEXA) (Hologic)	From baseline at week 0 to week 24
Secondary	Changes in Body Composition as Assessed by Body Fat Mass Using Dual Energy X-ray Absorptiometry (DEXA)	Body composition change between baseline and the end of the 24-week randomized drug treatment phase assessed by dual energy x-ray absorptiometry (DEXA) and expressed as the change in fat mass.	From baseline at week 0 to week 24
Secondary	Change in energy intake of test meal	The food intake will be assessed objectively by use of a feeding table. The test meal will be provided as lunch, and food types available on the table include staples, vegetables, mushrooms, meat, soy products, desserts, beverages and water. All types of food are unlimited. Food consumption will be recorded continuously by balances concealed under each food dish. The food energy density for each food will be measured by bomb calorimetry in kJ/g, and energy intake will be calculated as the product of the grams of each food eaten multiplied by the respective energy density and then summed, as kJ.	From baseline at week 0 to week 24
Secondary	Changes in Fat and Total Calorie Intake Assessed by Free Buffet Meal Analysis	Changes in fat and total calorie intake during free buffet meals assessed at baseline and after 24-weeks of study drug treatment.	From baseline at week 0 to week 24
Secondary	Energy intake during ad libitum lunch	The food intake will be assessed objectively by use of a feeding table. The test meal will be provided as lunch, and food types available on the table include staples, vegetables, mushrooms, meat, soy products, desserts, beverages and water. All types of food are unlimited. Food consumption will be recorded continuously by balances concealed under each food dish. The food energy density for each food will be measured by bomb calorimetry in kJ/g, and energy intake will be calculated as the product of the grams of each food eaten multiplied by the respective energy density and then summed, as kJ.	From baseline at week 0 to week 24
Secondary	Body temperature from surface temperature of the forehead	Body temperature will be measured before and after feeding using a thermal imaging camera. The camera is directed at the forehead to measure the surface temperature.	From baseline at week 0 to week 24
Secondary	Body water	Body water will be measured by deuterium dilution. Subjects will attend in the lab after an overnight fast and provide a baseline urine sample. They will then drink a dose of deuterated water based on their body weight. Three and four hours after dosing a urine sample will be collected to measure the level of deuterium isotope in the body relative to the baseline. This increase allows measurement of the amount of water in the body that diluted the dose.	From baseline at week 0 to week 24
Secondary	Overall appetite score (OAS) before and after intake of a standardised meal	give a score from 0 to 100	From baseline at week 0 to week 24
Secondary	Mean postprandial rating - Hunger	give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced	From baseline at week 0 to week 24
Secondary	Mean postprandial rating - Fullness	give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced	From baseline at week 0 to week 24
Secondary	Mean postprandial rating - Satiety	give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced	From baseline at week 0 to week 24
Secondary	Mean postprandial rating - Prospective food consumption	give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced	From baseline at week 0 to week 24
Secondary	Change in physical functioning score	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: role-physical score	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: bodily pain score	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: general health score	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: vitality score	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: social functioning score	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: role-emotional score	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: mental health score	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: physical component summary	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Change in SF-36: mental component summary	Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.	From baseline at week 0 to week 24
Secondary	Subjects who achieve responder definition value for SF-36 physical functioning score (yes/no)	Number of subjects	From baseline at week 0 to week 24
Secondary	Change in HbA1c	mmol /mol	From baseline at week 0 to week 24
Secondary	Change in systolic and diastolic blood pressure	Systolic and diastolic blood pressure will be measured using an Omron digital sphygmomanometer, as mmHg.	From baseline at week 0 to week 24
Secondary	Blood glucose	Fasting and post-prandial glucose after a standard meal will be recorded by a continuous glucose monitoring system.	From baseline at week 0 to week 24
Secondary	Change in fasting serum insulin	mIU/L	From baseline at week 0 to week 24
Secondary	Change in lipids: Total cholesterol	mg/dL	From baseline at week 0 to week 24
Secondary	Change in lipids: High density lipoprotein (HDL) cholesterol	mg/dL	From baseline at week 0 to week 24
Secondary	Change in lipids: Low density lipoprotein (LDL) cholesterol	mg/dL	From baseline at week 0 to week 24
Secondary	Change in lipids: Very low density lipoprotein (VLDL) cholesterol	mg/dL	From baseline at week 0 to week 24
Secondary	Change in lipids: Free fatty acids (FFA)	mg/dL	From baseline at week 0 to week 24
Secondary	Change in lipids: Triglycerides	mg/dL	From baseline at week 0 to week 24
Secondary	Change in fatty liver index (FLI) score category	Below 30, equal to or above 30 and below 60, equal to or above 60	From baseline at week 0 to week 24
Secondary	Changes in Inflammation Assessed by C-reactive Protein (CRP)	Change in C-reactive protein (CRP) between baseline and the end of the 24-week randomized drug treatment phase	From baseline at week 0 to week 24
Secondary	Subjects who have permanently discontinued randomised trial product (yes/no)	Number of subjects	From baseline at week 0 to week 24
Secondary	Time to permanent discontinuation of randomised trial product	Weeks	From baseline at week 0 to week 24
Secondary	Number of treatment emergent adverse events (TEAEs)	Count	From baseline at week 0 to week 24
Secondary	Number of serious adverse events (SAEs)	Count	From baseline at week 0 to week 24
Secondary	Change in pulse	Beats per minute (bpm)	From baseline at week 0 to week 24
Secondary	Change in amylase	U/L	From baseline at week 0 to week 24
Secondary	Change in lipase	U/L	From baseline at week 0 to week 24
Secondary	Changes of Circulating Leptin Levels	Change in circulating leptin between baseline and the end of the 24-week randomized drug treatment phase	From baseline at week 0 to week 24
Secondary	Circulating hormones	Nurses will collect the blood samples every month. Levels of circulating hormones (including leptin, insulin, ghrelin etc) and metabolic fuels (glycogen, lactate glucose etc) will be measured when fasted and after a standard intervention meal. Levels of circulating hormones in the serum will be measured by ELISA (Bio Tek, Synergy4) in mmol/L.	From baseline at week 0 to week 24
Secondary	Microbiome	Abundance of gut microbiome will be from Metagenomic profiling of feces by Illumina.	From baseline at week 0 to week 24
Secondary	Metabolites in serum, feces and urine	Abundance of metabolites will be from metabolomic profiling of serum, urine and feces by LC-MS (liquid chromatography-mass spectrometry).	From baseline at week 0 to week 24
Secondary	Genetics	Polymorphic variation will be assessed in a panel of SNPs (single nucleotide polymorphism) previously linked to body composition and physical activity using a Mass array sequencer.; OR The subjects will have their venous blood collected in a fasted state. 4ml of venous blood (BD vacutainer K2 EDTA, BD, USA) will be used to extract genomic DNA (TIANamp Blood DNA kit, TIANGEN, China. QIAamp Midi Blood DNA kit, QIAGEN, Germany) for Single nucleotide polymorphism (SNP) genotyping (Agena MassARRAY, CapitalBio Technology, China).	From baseline at week 0 to week 24