Brown Adipose Tissue as a Mechanistic Determinant of GLP-1 Receptor Agonist Treatment Response in Adults With Obesity: A Multicenter Prospective Cohort Study Using ¹⁸FDG-PET/CT and Cold Stimulation Protocol
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 80
- 试验地点
- 2
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 20-70 years at the time of enrollment
- •Initiating semaglutide (Wegovy) treatment for obesity (newly starting treatment)
- •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)
- •Ability and willingness to provide written informed consent
排除标准
- •Diagnosis of type 1 or type 2 diabetes mellitus
- •History of neck surgery or radiation therapy to the neck
- •Use of anti-obesity medications within 1 month prior to enrollment, or current use of beta-adrenergic blocking agents
- •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2)
- •Active malignancy, severe renal disease (eGFR <30 mL/min/1.73m²), severe hepatic disease, or other severe endocrine disorders
- •Pregnancy or breastfeeding
- •Severe psychiatric illness or cognitive impairment precluding informed consent
- •Contraindication to MRI (pacemaker, cochlear implant, non-MRI-compatible implants)
- •Severe claustrophobia
研究组 & 干预措施
Semaglutide + BAT Evaluation
Adults with obesity initiating semaglutide (0.25 mg → 2.4 mg over 20 weeks, maintained for 4 weeks; total 24 weeks). At baseline and 24 weeks, ¹⁸FDG-PET/CT with individualized cold stimulation (water-circulating cooling vest at 16°C, 60 minutes) and liver MRI (PDFF + MRE) are performed.
干预措施: Liver MRI (PDFF + MRE) (Procedure)
Semaglutide + BAT Evaluation
Adults with obesity initiating semaglutide (0.25 mg → 2.4 mg over 20 weeks, maintained for 4 weeks; total 24 weeks). At baseline and 24 weeks, ¹⁸FDG-PET/CT with individualized cold stimulation (water-circulating cooling vest at 16°C, 60 minutes) and liver MRI (PDFF + MRE) are performed.
干预措施: Semaglutide (Wegovy®) (Drug)
Semaglutide + BAT Evaluation
Adults with obesity initiating semaglutide (0.25 mg → 2.4 mg over 20 weeks, maintained for 4 weeks; total 24 weeks). At baseline and 24 weeks, ¹⁸FDG-PET/CT with individualized cold stimulation (water-circulating cooling vest at 16°C, 60 minutes) and liver MRI (PDFF + MRE) are performed.
干预措施: ¹⁸FDG-PET/CT with cold stimulation (Procedure)
研究者
Hun Jee Choe
Assistant Professor, Division of Endocrinology and Metabolism
Hallym University Dongtan Sacred Heart Hospital