Brown Adipose Tissue, Metabolic Syndrome, Obesity
Conditions
Keywords
Brown adipose tissue, Semaglutide, GLP-1 receptor agonist, Obesity, FDG-PET/CT, BAT, Biomarker, Weight loss, PDFF
Brief summary
This study investigates whether the activity of brown adipose tissue (BAT) - a special type of fat that burns energy as heat - can predict how well individuals with obesity respond to semaglutide (Wegovy), a once-weekly injectable weight loss medication. Participants who are starting semaglutide treatment will undergo ¹⁸FDG-PET/CT imaging before and after 24 weeks of treatment. Prior to each PET/CT scan, participants will wear a water-circulating cooling vest to activate BAT. By measuring BAT activity at baseline and comparing it with the degree of weight loss and metabolic improvement at 24 weeks, the investigators aim to identify BAT as a predictive biomarker for personalized obesity treatment.
Detailed description
Despite the remarkable efficacy of semaglutide (GLP-1 receptor agonist) in treating obesity, considerable individual variation in treatment response remains unexplained. Brown adipose tissue (BAT) is a metabolically active thermogenic organ that has been implicated in energy expenditure, insulin sensitivity, and cardiometabolic health. We hypothesize that baseline BAT activity, as measured by ¹⁸FDG-PET/CT following individualized cold stimulation, is a mechanistic determinant of semaglutide treatment response in adults with obesity without diabetes. This multicenter prospective cohort study will enroll 80 adults (40 per site: Hallym University Dongtan Sacred Heart Hospital and Seoul National University Bundang Hospital) with BMI ≥27 kg/m² plus obesity-related comorbidity, or BMI ≥30 kg/m², who are initiating semaglutide therapy. ¹⁸FDG-PET/CT with standardized cold stimulation (water-circulating cooling vest, starting at 16°C, individualized to prevent shivering) will be performed at baseline (V1) and 24 weeks (V7). BAT activity (SUVmax, SUVmean, BAT volume, total metabolic activity) will be quantified per BARCIST 1.0 criteria. Liver fat fraction (MRI-PDFF) and liver stiffness (MR elastography) will be assessed as secondary endpoints. Correlations between baseline BAT parameters and treatment outcomes (% body weight loss, metabolic biomarker changes) will be analyzed.
Interventions
DRUGSemaglutide (Wegovy®)
Once-weekly subcutaneous injection, titrated from 0.25 mg to 2.4 mg over 20 weeks per standard protocol. Standard of care treatment for obesity.
PROCEDURE¹⁸FDG-PET/CT with cold stimulation
Whole-body ¹⁸FDG-PET/CT (5.18 MBq/kg, max 370 MBq) after 60-minute individualized cold stimulation using a water-circulating cooling vest (Polar Products Arctic Chiller, starting 16°C). Performed at baseline (V1) and 24 weeks (V7). BAT activity quantified per BARCIST 1.0.
PROCEDURELiver MRI (PDFF + MRE)
Hepatic proton density fat fraction (MRI-PDFF) and liver stiffness by MR elastography (MRE) using Siemens MAGNETOM Vida 3T. Performed at baseline (V1) and 24 weeks (V7).
Sponsors
Hallym University
Hallym University Dongtan Sacred Heart Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Single-arm prospective mechanistic cohort study evaluating the association between baseline brown adipose tissue activity and semaglutide treatment response in adults with obesity using individualized cold-stimulated ¹⁸FDG-PET/CT.
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 20-70 years at the time of enrollment 2. Initiating semaglutide (Wegovy) treatment for obesity (newly starting treatment) 3. BMI ≥ 27 kg/m² with at least one weight-related comorbidity: * Hypertension (SBP ≥130 or DBP ≥80 mmHg, or on antihypertensive medication) * Dyslipidemia (LDL-C ≥130, TG ≥150, or low HDL-C, or on lipid-lowering medication) * Non-alcoholic fatty liver disease (NAFLD/MASLD, confirmed by imaging or ALT/AST ≥1.5× ULN) * Obstructive sleep apnea (AHI ≥5/hr or clinically diagnosed) * Established cardiovascular disease (CAD, stroke, PAD) * Obesity-related osteoarthritis of knee or hip with functional impairment OR BMI ≥ 30 kg/m² (regardless of comorbidity) 4. Ability and willingness to provide written informed consent
Exclusion criteria
1. Diagnosis of type 1 or type 2 diabetes mellitus 2. History of neck surgery or radiation therapy to the neck 3. Use of anti-obesity medications within 1 month prior to enrollment, or current use of beta-adrenergic blocking agents 4. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2) 5. Active malignancy, severe renal disease (eGFR \<30 mL/min/1.73m²), severe hepatic disease, or other severe endocrine disorders 6. Pregnancy or breastfeeding 7. Severe psychiatric illness or cognitive impairment precluding informed consent 8. Contraindication to MRI (pacemaker, cochlear implant, non-MRI-compatible implants) 9. Severe claustrophobia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between baseline BAT metabolic activity (SUVmean and BAT volume on ¹⁸FDG-PET/CT) and percentage body weight loss at 24 weeks of semaglutide treatment | Baseline to 24 weeks | : Pearson (or Spearman) correlation coefficient between baseline BAT parameters (SUVmean, BAT volume, total metabolic activity per BARCIST 1.0) and % body weight loss after 24 weeks of semaglutide therapy (0.25 mg escalated to 2.4 mg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in waist circumference | Baseline to 24 weeks | — |
| Change in body weight (kg) | Baseline to 24 weeks | — |
| Change in Body Mass Index (BMI) | Baseline to 24 weeks | — |
| Change in HbA1c (%) | Baseline to 24 weeks | — |
| Change in fasting glucose (mg/dL) | Baseline to 24 weeks | — |
| Change in HOMA-IR | Baseline to 24 weeks | — |
| Change in fasting lipids (LDL-C, HDL-C, TG, TC) | Baseline to 24 weeks | — |
| Change in body composition by BIA (fat mass, lean mass, skeletal muscle mass) | Baseline to 24 weeks | — |
| Change in liver fat fraction (MRI-PDFF, %) | Baseline to 24 weeks | — |
| Change in liver stiffness by MRE (kPa) | Baseline to 24 weeks | — |
| Change in adipokines (adiponectin, leptin, NEFA) | Baseline to 24 weeks | — |
| Change in hsCRP | Baseline to 24 weeks | — |
| BAT-positive rate based on SUVmax at baseline | Baseline | The percentage of participants determined as brown adipose tissue (BAT)-positive, defined by a maximum standardized uptake value (SUVmax) of 1.5 or higher ($\\ge 1.5$) at baseline. |
| Change in Quality of life using the Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) total score | Baseline to 24 weeks | The Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) is a self-report questionnaire used to assess the quality of life in individuals with obesity. The total score ranges from a minimum of 0 to a maximum of 100, where higher scores indicate a better outcome (better quality of life). |
| Change in Quality of Life using the Short Form-36 Health Survey Version 2 (SF-36v2) domain scores | Baseline to 24 weeks | The Short Form-36 Health Survey Version 2 (SF-36v2) is a 36-item questionnaire measuring health-related quality of life across 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Each domain score ranges from a minimum of 0 to a maximum of 100, where higher scores indicate a better outcome (better health status or higher quality of life). |
| Change in BAT activity (SUVmax, SUVmean, BAT volume, TMA) from baseline to 24 weeks | Baseline to 24 weeks | — |
| BAT-positive rate based on CT Hounsfield Units (HU) at baseline | Baseline | The percentage of participants determined as brown adipose tissue (BAT)-positive, defined by Computed Tomography Hounsfield Units (CT HU) within the range of $-250$ to $-50$ at baseline. |
Countries
South Korea
Contacts
CONTACTHun Jee Choe Hallym University Dongtan Sacred Heart Hospital, MD, PhD
CONTACTHye Jeong Lee Hallym University Dongtan Sacred Heart Hospital, CRC
Outcome results
None listed