Comparative Observation of Metabolic and Pharmacologic Adipose Remodeling With Enhanced Incretin AgonisTs (COMPARE-AT)
Comparative Adipose Tissue and Cardiometabolic System Remodeling by Tirzepatide and Semaglutide: an AI-integrated Multimodal Metabolomics and Translational Mechanistic Study
調査の概要
状態
詳細な説明
This study is a single-center, randomized, open-label, active-comparator trial designed to characterize the differential effects of tirzepatide and semaglutide on adipose tissue biology and cardiometabolic remodeling over 12 months in adults with obesity and metabolic syndrome. The trial integrates pharmacologic weight-loss therapy with multimodal phenotyping to quantify changes across body composition, hepatic steatosis, metabolic biomarkers, functional strength, and AI-derived electrophysiologic signatures.
The scientific premise is that incretin-based therapies may produce qualitatively distinct patterns of fat loss, ectopic fat mobilization, and cardiometabolic improvement. Tirzepatide, a dual GIP/GLP-1 receptor agonist, may induce greater reductions in visceral adiposity and hepatic fat compared with GLP-1 receptor agonism alone. This trial is designed to directly compare these mechanistic profiles using harmonized imaging, biochemical, and digital phenotyping platforms.
Participants are randomized 1:1 to tirzepatide or semaglutide using a computer-generated permuted block scheme stratified by sex and baseline BMI category. Both interventions follow standard titration schedules and are paired with structured lifestyle counseling to ensure comparable background care. Study visits occur at baseline, 3, 6, and 12 months, with deep phenotyping at baseline, 6, and 12 months.
The phenotyping framework emphasizes regional adiposity, lean mass preservation, hepatic steatosis, and cardiometabolic risk signatures. Whole-body DXA provides quantification of total and regional fat and lean mass, enabling derivation of fat-to-lean mass loss ratios and redistribution indices. Abdominal MRI with proton density fat fraction (PDFF) quantifies liver fat content and abdominal fat compartments. Functional and behavioral assessments-including grip strength and the Chinese version of the Weight-Related Eating Questionnaire-characterize changes in physical function and eating behavior patterns over time.
Fasting biochemical panels measure glycemic indices, lipid metabolism, inflammation, renal and hepatic function, and cardiometabolic biomarkers. Standard 12-lead ECGs are processed through a validated AI pipeline to generate electrophysiologic risk features (e.g., predicted ASCVD risk, ECG-derived heart age), which serve as exploratory digital biomarkers.
A centralized biobanking program supports mechanistic analyses. Serum, plasma, and PBMCs collected at each deep-phenotyping visit are stored under standardized SOPs for targeted and discovery-based metabolomic, proteomic, epigenetic and transcriptomic analyses. These biospecimens will enable downstream investigation of molecular pathways underlying differential treatment responses.
Together, this integrated platform allows for a comprehensive comparison of tirzepatide and semaglutide across structural, metabolic, functional, and molecular domains, providing mechanistic insight into how incretin-based therapies remodel adipose tissue and cardiometabolic physiology.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Feng-Chih Kuo, M.D., Ph.D.
- 電話番号：12687 886-2-87923311
- メール：shoummie@hotmail.com
研究場所
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Taipei、台湾、114202
- 募集
- Tri-Service General Hospital
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コンタクト：
- Feng-Chih Kuo, M.D., Ph.D.
- 電話番号：12687 886-2-87923311
- メール：shoummie@hotmail.com
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Age 20-65 years.
- BMI ≥27 kg/m² with metabolic syndrome (ATP III or IDF criteria).
- Stable background medications (antihypertensives, statins, etc.) for ≥3 months.
- Able and willing to provide informed consent and comply with study procedures.
Exclusion Criteria:
- History of diabetes; history of pancreatitis; personal/family history of medullary thyroid carcinoma or MEN2.
- eGFR <30 mL/min/1.73 m², decompensated liver disease, NYHA class III-IV heart failure.
- Recent (<3 months) acute coronary syndrome, stroke, or coronary revascularization.
- Current use of GLP 1RA, tirzepatide, or other incretin based therapies within 3 months.
- Contraindications to MRI or DXA (e.g., metal implants incompatible with MRI, pregnancy).
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：Tirzepatide arm
starting at 2.5 mg weekly and escalated every month (5.0 mg, 7.5 mg to 10 mg) as tolerated
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Starting at Tirzepatide 2.5 mg weekly and escalated as tolerated to 10 mg along with standardized lifestyle counseling by a dietitian (caloric deficit, physical activity guidance) and written materials.
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アクティブコンパレータ：Semaglutide arm
starting at 0.25 mg weekly and escalated every month (0.5 mg, 1.0 mg, 1.7 mg to 2.4 mg) as tolerated
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Starting at Semaglutide 0.25 mg weekly and escalated as tolerated to 2.4 mg along with standardized lifestyle counseling by a dietitian (caloric deficit, physical activity guidance) and written materials.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
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Percent change in total body weight from baseline to 6 months.
時間枠：Baseline to 6 months
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Baseline to 6 months
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Total fat to lean mass loss ratio (DXA derived) from baseline to 6 months.
時間枠：Baseline to 6 months
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Baseline to 6 months
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Change in metabolic syndrome severity Z score from baseline to 6 months.
時間枠：Baseline to 6 months.
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Baseline to 6 months.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in waist circumference (cm)
時間枠：Baseline to 6 months and 12 months
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Baseline to 6 months and 12 months
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Change in waist-to-hip ratio (unitless ratio)
時間枠：Baseline to 6 months and 12 months.
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Baseline to 6 months and 12 months.
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Change in regional fat mass measured by DXA (grams)
時間枠：Baseline to 6 months and 12 months.
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Baseline to 6 months and 12 months.
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Change in regional lean mass measured by DXA (grams)
時間枠：Baseline to 6 months and 12 months
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Baseline to 6 months and 12 months
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Change in 7-site skinfold thickness (mm)
時間枠：Baseline to 6 months and 12 months.
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Baseline to 6 months and 12 months.
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Change in liver fat content measured by MRI-PDFF (percentage, %PDFF)
時間枠：Baseline to 6 months and 12 months
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Baseline to 6 months and 12 months
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Change in abdominal visceral fat volume (mL)
時間枠：Baseline to 6 months and 12 months
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Baseline to 6 months and 12 months
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Change in abdominal subcutaneous fat volume (mL)
時間枠：Baseline to 6 months and 12 months
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Baseline to 6 months and 12 months
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Change in systolic and diastolic blood pressure (mmHg)
時間枠：Baseline to 6 months and 12 months
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Baseline to 6 months and 12 months
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Change in fasting lipid profile (mg/dL)
時間枠：Baseline to 6 months and 12 months
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Lipid profile includes total cholesterol, LDL-C, HDL-C and Triglycerides
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Baseline to 6 months and 12 months
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Change in fasting glucose (mg/dL)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in hsCRP (mg/L)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in insulin sensitivity (HOMA-IR, unitless)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in β-cell function (HOMA-β, percentage, %)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in AI-ECG predicted ASCVD risk score (percentage, %)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in ECG-derived heart age (years)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in AI-ECG diabetes risk index (HbA1c, percentage, %)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in estimated 10-year ASCVD risk (percentage, %)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in bone mineral density (g/cm²)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in serum P1NP (ng/mL)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in serum CTX-1 (ng/mL)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in fasting plasma metabolomics profile (relative abundance units)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in fasting plasma proteomics profile (relative abundance units)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in microRNA expression signatures (normalized expression units)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in RNA-seq transcriptomic signatures (normalized counts, e.g., TPM)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in epigenetic methylation signatures (Methylation, percentage, %)
時間枠：Baseline to 6 and 12 months
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Baseline to 6 and 12 months
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Change in depressive symptoms (scale score)
時間枠：Baseline to 6 and 12 months
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Instrument: e.g., PHQ-9
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Baseline to 6 and 12 months
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Change in sleep quality (scale score)
時間枠：Baseline to 6 and 12 months
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Instrument: e.g., PSQI
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Baseline to 6 and 12 months
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Change in quality of life (scale score)
時間枠：Baseline to 6 and 12 months
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Instrument: e.g., EQ-5D or SF-36
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Baseline to 6 and 12 months
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Change in eating behavior (WREQ-C total and subscale scores)
時間枠：Baseline to 3, 6, and 12 months
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Baseline to 3, 6, and 12 months
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協力者と研究者
捜査官
- スタディディレクター：Feng-Chih Kuo, M.D., Ph.D.、Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- C202505161
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