- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06390501
The Effect of Weekly Semaglutide Treatment on Energy Expenditure
Study Overview
Detailed 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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: John R Speakman, phD
- Phone Number: 13466654659
- Email: j.speakman@abdn.ac.uk
Study Contact Backup
- Name: huihui mei
- Phone Number: 17852427660
- Email: hh.mei@siat.ac.cn
Study Locations
-
-
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Shenzhen, China
- Recruiting
- Shenzhen Institute of Advanced Technology
-
Contact:
- John R Speakman
- Phone Number: 13466654659
- Email: j.speakman@abdn.ac.uk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion criteria:
- Age 18-60 years at time of enrollment
- BMI ≥ 25 kg/m²
Exclusion criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Semaglutide
Once-weekly injections of gradually increased doses of 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 Comparator: Placebo
Once-weekly injections of gradually increased volumes of saline placebo, to match the volumes of the semaglutide treated arm.
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Solution for subcutaneous (s.c. - under the skin) injection
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes of Total Energy Expenditure Assessed by Doubly Labeled Water Analysis
Time Frame: 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.
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From baseline at week 0 to week 24
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Changes of Energy Expenditure Assessed by Chamber
Time Frame: From baseline at week 0 to week 24
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The total energy expenditure in a free living environment is measured using a 24-hour chamber.
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From baseline at week 0 to week 24
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Changes of Resting Energy Expenditure
Time Frame: From baseline at week 0 to week 24
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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
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Changes of Physical Activity
Time Frame: 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.
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From baseline at week 0 to week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Body Weight
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Body Mass Index (BMI)
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Waist and Hip circumferences
Time Frame: From baseline at week 0 to week 24
|
Waist and Hip circumferences will be measured using a whole body laser scanner.
|
From baseline at week 0 to week 24
|
Body shape
Time Frame: From baseline at week 0 to week 24
|
Body shape will be measured using a whole body laser scanner.
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From baseline at week 0 to week 24
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Fat mass
Time Frame: From baseline at week 0 to week 24
|
Fat mass will be measured by Magnetic Resonance Imaging (Shanghai united imaging, uMR 790 ).
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From baseline at week 0 to week 24
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Far free mass
Time Frame: From baseline at week 0 to week 24
|
Fat free mass will be measured by Bioimpedance Analysis (Tanita, MC-980).
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From baseline at week 0 to week 24
|
Organ sizes
Time Frame: From baseline at week 0 to week 24
|
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 ).
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From baseline at week 0 to week 24
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Bone mass
Time Frame: From baseline at week 0 to week 24
|
Bone mass will be measured by Dual Energy X-ray Absorptiometry (DEXA) (Hologic)
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From baseline at week 0 to week 24
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Changes in Body Composition as Assessed by Body Fat Mass Using Dual Energy X-ray Absorptiometry (DEXA)
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Change in energy intake of test meal
Time Frame: From baseline at week 0 to week 24
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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.
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From baseline at week 0 to week 24
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Changes in Fat and Total Calorie Intake Assessed by Free Buffet Meal Analysis
Time Frame: From baseline at week 0 to week 24
|
Changes in fat and total calorie intake during free buffet meals assessed at baseline and after 24-weeks of study drug treatment.
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From baseline at week 0 to week 24
|
Energy intake during ad libitum lunch
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Body temperature from surface temperature of the forehead
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Body water
Time Frame: From baseline at week 0 to week 24
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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.
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From baseline at week 0 to week 24
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Overall appetite score (OAS) before and after intake of a standardised meal
Time Frame: From baseline at week 0 to week 24
|
give a score from 0 to 100
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From baseline at week 0 to week 24
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Mean postprandial rating - Hunger
Time Frame: From baseline at week 0 to week 24
|
give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced
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From baseline at week 0 to week 24
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Mean postprandial rating - Fullness
Time Frame: From baseline at week 0 to week 24
|
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
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Mean postprandial rating - Satiety
Time Frame: From baseline at week 0 to week 24
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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
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Mean postprandial rating - Prospective food consumption
Time Frame: From baseline at week 0 to week 24
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give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced
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From baseline at week 0 to week 24
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Change in physical functioning score
Time Frame: From baseline at week 0 to week 24
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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.
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From baseline at week 0 to week 24
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Change in SF-36: role-physical score
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Change in SF-36: bodily pain score
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Change in SF-36: general health score
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Change in SF-36: vitality score
Time Frame: From baseline at week 0 to week 24
|
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
|
Change in SF-36: social functioning score
Time Frame: From baseline at week 0 to week 24
|
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.
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From baseline at week 0 to week 24
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Change in SF-36: role-emotional score
Time Frame: From baseline at week 0 to week 24
|
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
|
Change in SF-36: mental health score
Time Frame: From baseline at week 0 to week 24
|
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
|
Change in SF-36: physical component summary
Time Frame: From baseline at week 0 to week 24
|
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
|
Change in SF-36: mental component summary
Time Frame: From baseline at week 0 to week 24
|
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
|
Subjects who achieve responder definition value for SF-36 physical functioning score (yes/no)
Time Frame: From baseline at week 0 to week 24
|
Number of subjects
|
From baseline at week 0 to week 24
|
Change in HbA1c
Time Frame: From baseline at week 0 to week 24
|
mmol /mol
|
From baseline at week 0 to week 24
|
Change in systolic and diastolic blood pressure
Time Frame: From baseline at week 0 to week 24
|
Systolic and diastolic blood pressure will be measured using an Omron digital sphygmomanometer, as mmHg.
|
From baseline at week 0 to week 24
|
Blood glucose
Time Frame: From baseline at week 0 to week 24
|
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
|
Change in fasting serum insulin
Time Frame: From baseline at week 0 to week 24
|
mIU/L
|
From baseline at week 0 to week 24
|
Change in lipids: Total cholesterol
Time Frame: From baseline at week 0 to week 24
|
mg/dL
|
From baseline at week 0 to week 24
|
Change in lipids: High density lipoprotein (HDL) cholesterol
Time Frame: From baseline at week 0 to week 24
|
mg/dL
|
From baseline at week 0 to week 24
|
Change in lipids: Low density lipoprotein (LDL) cholesterol
Time Frame: From baseline at week 0 to week 24
|
mg/dL
|
From baseline at week 0 to week 24
|
Change in lipids: Very low density lipoprotein (VLDL) cholesterol
Time Frame: From baseline at week 0 to week 24
|
mg/dL
|
From baseline at week 0 to week 24
|
Change in lipids: Free fatty acids (FFA)
Time Frame: From baseline at week 0 to week 24
|
mg/dL
|
From baseline at week 0 to week 24
|
Change in lipids: Triglycerides
Time Frame: From baseline at week 0 to week 24
|
mg/dL
|
From baseline at week 0 to week 24
|
Change in fatty liver index (FLI) score category
Time Frame: From baseline at week 0 to week 24
|
Below 30, equal to or above 30 and below 60, equal to or above 60
|
From baseline at week 0 to week 24
|
Changes in Inflammation Assessed by C-reactive Protein (CRP)
Time Frame: From baseline at week 0 to week 24
|
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
|
Subjects who have permanently discontinued randomised trial product (yes/no)
Time Frame: From baseline at week 0 to week 24
|
Number of subjects
|
From baseline at week 0 to week 24
|
Time to permanent discontinuation of randomised trial product
Time Frame: From baseline at week 0 to week 24
|
Weeks
|
From baseline at week 0 to week 24
|
Number of treatment emergent adverse events (TEAEs)
Time Frame: From baseline at week 0 to week 24
|
Count
|
From baseline at week 0 to week 24
|
Number of serious adverse events (SAEs)
Time Frame: From baseline at week 0 to week 24
|
Count
|
From baseline at week 0 to week 24
|
Change in pulse
Time Frame: From baseline at week 0 to week 24
|
Beats per minute (bpm)
|
From baseline at week 0 to week 24
|
Change in amylase
Time Frame: From baseline at week 0 to week 24
|
U/L
|
From baseline at week 0 to week 24
|
Change in lipase
Time Frame: From baseline at week 0 to week 24
|
U/L
|
From baseline at week 0 to week 24
|
Changes of Circulating Leptin Levels
Time Frame: From baseline at week 0 to week 24
|
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
|
Circulating hormones
Time Frame: From baseline at week 0 to week 24
|
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
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Microbiome
Time Frame: From baseline at week 0 to week 24
|
Abundance of gut microbiome will be from Metagenomic profiling of feces by Illumina.
|
From baseline at week 0 to week 24
|
Metabolites in serum, feces and urine
Time Frame: From baseline at week 0 to week 24
|
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
|
Genetics
Time Frame: From baseline at week 0 to week 24
|
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
|
Collaborators and Investigators
Investigators
- Study Chair: John R Speakman, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SIAT-IRB-231215-H0705
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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