Clinical trial NCT06390501: The Effect of Weekly Semaglutide Treatment on Energy Expenditure
Official title: The Effect of Weekly Semaglutide Treatment on Energy Expenditure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity; Drug
Lead sponsor: Shenzhen Institutes of Advanced Technology ,Chinese Academy of Sciences
Sponsor class: OTHER
First posted: 2024-04-30
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes of Total Energy Expenditure Assessed by Doubly Labeled Water Analysis
timeFrame: From baseline at week 0 to week 24
measure: Changes of Energy Expenditure Assessed by Chamber
timeFrame: From baseline at week 0 to week 24
measure: Changes of Resting Energy Expenditure
timeFrame: From baseline at week 0 to week 24
measure: Changes of Physical Activity
timeFrame: From baseline at week 0 to week 24
Secondary outcomes:
measure: Body Weight
timeFrame: From baseline at week 0 to week 24
measure: Body Mass Index (BMI)
timeFrame: From baseline at week 0 to week 24
measure: Waist and Hip circumferences
timeFrame: From baseline at week 0 to week 24
measure: Body shape
timeFrame: From baseline at week 0 to week 24
measure: Fat mass
timeFrame: From baseline at week 0 to week 24
measure: Far free mass
timeFrame: From baseline at week 0 to week 24
measure: Organ sizes
timeFrame: From baseline at week 0 to week 24
measure: Bone mass
timeFrame: From baseline at week 0 to week 24
measure: Changes in Body Composition as Assessed by Body Fat Mass Using Dual Energy X-ray Absorptiometry (DEXA)
timeFrame: From baseline at week 0 to week 24
measure: Change in energy intake of test meal
timeFrame: From baseline at week 0 to week 24
measure: Changes in Fat and Total Calorie Intake Assessed by Free Buffet Meal Analysis
timeFrame: From baseline at week 0 to week 24
measure: Energy intake during ad libitum lunch
timeFrame: From baseline at week 0 to week 24
measure: Body temperature from surface temperature of the forehead
timeFrame: From baseline at week 0 to week 24
measure: Body water
timeFrame: From baseline at week 0 to week 24
measure: Overall appetite score (OAS) before and after intake of a standardised meal
timeFrame: From baseline at week 0 to week 24
measure: Mean postprandial rating - Hunger
timeFrame: From baseline at week 0 to week 24
measure: Mean postprandial rating - Fullness
timeFrame: From baseline at week 0 to week 24
measure: Mean postprandial rating - Satiety
timeFrame: From baseline at week 0 to week 24
measure: Mean postprandial rating - Prospective food consumption
timeFrame: From baseline at week 0 to week 24
measure: Change in physical functioning score
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: role-physical score
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: bodily pain score
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: general health score
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: vitality score
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: social functioning score
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: role-emotional score
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: mental health score
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: physical component summary
timeFrame: From baseline at week 0 to week 24
measure: Change in SF-36: mental component summary
timeFrame: From baseline at week 0 to week 24
measure: Subjects who achieve responder definition value for SF-36 physical functioning score (yes/no)
timeFrame: From baseline at week 0 to week 24
measure: Change in HbA1c
timeFrame: From baseline at week 0 to week 24
measure: Change in systolic and diastolic blood pressure
timeFrame: From baseline at week 0 to week 24
measure: Blood glucose
timeFrame: From baseline at week 0 to week 24
measure: Change in fasting serum insulin
timeFrame: From baseline at week 0 to week 24
measure: Change in lipids: Total cholesterol
timeFrame: From baseline at week 0 to week 24
measure: Change in lipids: High density lipoprotein (HDL) cholesterol
timeFrame: From baseline at week 0 to week 24
measure: Change in lipids: Low density lipoprotein (LDL) cholesterol
timeFrame: From baseline at week 0 to week 24
measure: Change in lipids: Very low density lipoprotein (VLDL) cholesterol
timeFrame: From baseline at week 0 to week 24
measure: Change in lipids: Free fatty acids (FFA)
timeFrame: From baseline at week 0 to week 24
measure: Change in lipids: Triglycerides
timeFrame: From baseline at week 0 to week 24
measure: Change in fatty liver index (FLI) score category
timeFrame: From baseline at week 0 to week 24
measure: Changes in Inflammation Assessed by C-reactive Protein (CRP)
timeFrame: From baseline at week 0 to week 24
measure: Subjects who have permanently discontinued randomised trial product (yes/no)
timeFrame: From baseline at week 0 to week 24
measure: Time to permanent discontinuation of randomised trial product
timeFrame: From baseline at week 0 to week 24
measure: Number of treatment emergent adverse events (TEAEs)
timeFrame: From baseline at week 0 to week 24
measure: Number of serious adverse events (SAEs)
timeFrame: From baseline at week 0 to week 24
measure: Change in pulse
timeFrame: From baseline at week 0 to week 24
measure: Change in amylase
timeFrame: From baseline at week 0 to week 24
measure: Change in lipase
timeFrame: From baseline at week 0 to week 24
measure: Changes of Circulating Leptin Levels
timeFrame: From baseline at week 0 to week 24
measure: Circulating hormones
timeFrame: From baseline at week 0 to week 24
measure: Microbiome
timeFrame: From baseline at week 0 to week 24
measure: Metabolites in serum, feces and urine
timeFrame: From baseline at week 0 to week 24
measure: Genetics
timeFrame: From baseline at week 0 to week 24
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Institute of Advanced Technology
Study officials:
affiliation: Shenzhen Institutes of Advanced Technology ,Chinese Academy of Sciences
name: John R Speakman
role: STUDY_CHAIR
References: