Brown Adipose Tissue as a Mechanistic Determinant of Semaglutide Treatment Response in Obesity (BAT-Sema Study)

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Semaglutide (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.
• Процедура ¹⁸FDG-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.
• Процедура Liver 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).

Первичные конечные точки

• 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 [Срок оценки: Baseline to 24 weeks]

Вторичные конечные точки (12)

• Change in waist circumference [Срок оценки: Baseline to 24 weeks]
• Change in body weight (kg) [Срок оценки: Baseline to 24 weeks]
• Change in Body Mass Index (BMI) [Срок оценки: Baseline to 24 weeks]
• Change in HbA1c (%) [Срок оценки: Baseline to 24 weeks]
• Change in fasting glucose (mg/dL) [Срок оценки: Baseline to 24 weeks]
• Change in HOMA-IR [Срок оценки: Baseline to 24 weeks]
• Change in fasting lipids (LDL-C, HDL-C, TG, TC) [Срок оценки: Baseline to 24 weeks]
• Change in body composition by BIA (fat mass, lean mass, skeletal muscle mass) [Срок оценки: Baseline to 24 weeks]
• Change in liver fat fraction (MRI-PDFF, %) [Срок оценки: Baseline to 24 weeks]
• Change in liver stiffness by MRE (kPa) [Срок оценки: Baseline to 24 weeks]
• Change in adipokines (adiponectin, leptin, NEFA) [Срок оценки: Baseline to 24 weeks]
• Change in hsCRP [Срок оценки: Baseline to 24 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

South Korea · 2 центра

• Hallym University Dongtan Sacred Heart Hospital — Hwaseong-si
• Seoul National University Bundang Hospital — Seongnam-si

Идентификаторы

NCT: NCT07621640 · 2026-04-009 · RS-2026-25483260

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗