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Comparative Observation of Metabolic and Pharmacologic Adipose Remodeling With Enhanced Incretin AgonisTs (COMPARE-AT)

2026年5月10日 更新者：Feng-Chih Kuo、Tri-Service General Hospital

Comparative Adipose Tissue and Cardiometabolic System Remodeling by Tirzepatide and Semaglutide: an AI-integrated Multimodal Metabolomics and Translational Mechanistic Study

This randomized, open label, head to head clinical trial directly compares tirzepatide and semaglutide in adults with obesity and metabolic syndrome (N=120, age 20-65, 1:1 randomization). Participants undergo deep phenotyping at baseline, 6 months, and 12 months, including DXA (regional fat, lean mass, and BMD), MRI PDFF (liver fat), 7 site skinfold thickness, grip strength, fasting biochemistry, and AI processed 12 lead ECGs. Centralized biobanking of serum, plasma, and PBMCs enables targeted and discovery multi omic analyses.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

120

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

  • 姓名：Feng-Chih Kuo, M.D., Ph.D.
  • 电话号码：12687 886-2-87923311
  • 邮箱：shoummie@hotmail.com

学习地点

  • 台湾
      • Taipei、台湾、114202
        • 招聘中
        • Tri-Service General Hospital
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

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).

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
有源比较器：Tirzepatide arm
starting at 2.5 mg weekly and escalated every month (5.0 mg, 7.5 mg to 10 mg) as tolerated
药品：Tirzepatide with lifestyle modification
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.
有源比较器：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
药品：Semaglutide with lifestyle modification
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.

研究衡量的是什么？

主要结果指标

结果测量
大体时间
Percent change in total body weight from baseline to 6 months.
大体时间：Baseline to 6 months
Baseline to 6 months
Total fat to lean mass loss ratio (DXA derived) from baseline to 6 months.
大体时间：Baseline to 6 months
Baseline to 6 months
Change in metabolic syndrome severity Z score from baseline to 6 months.
大体时间：Baseline to 6 months.
Baseline to 6 months.

次要结果测量

结果测量
措施说明
大体时间
Change in waist circumference (cm)
大体时间：Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in waist-to-hip ratio (unitless ratio)
大体时间：Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in regional fat mass measured by DXA (grams)
大体时间：Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in regional lean mass measured by DXA (grams)
大体时间：Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in 7-site skinfold thickness (mm)
大体时间：Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in liver fat content measured by MRI-PDFF (percentage, %PDFF)
大体时间：Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in abdominal visceral fat volume (mL)
大体时间：Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in abdominal subcutaneous fat volume (mL)
大体时间：Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in systolic and diastolic blood pressure (mmHg)
大体时间：Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in fasting lipid profile (mg/dL)
大体时间：Baseline to 6 months and 12 months
Lipid profile includes total cholesterol, LDL-C, HDL-C and Triglycerides
Baseline to 6 months and 12 months
Change in fasting glucose (mg/dL)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in hsCRP (mg/L)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in insulin sensitivity (HOMA-IR, unitless)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in β-cell function (HOMA-β, percentage, %)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in AI-ECG predicted ASCVD risk score (percentage, %)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in ECG-derived heart age (years)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in AI-ECG diabetes risk index (HbA1c, percentage, %)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in estimated 10-year ASCVD risk (percentage, %)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in bone mineral density (g/cm²)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in serum P1NP (ng/mL)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in serum CTX-1 (ng/mL)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in fasting plasma metabolomics profile (relative abundance units)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in fasting plasma proteomics profile (relative abundance units)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in microRNA expression signatures (normalized expression units)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in RNA-seq transcriptomic signatures (normalized counts, e.g., TPM)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in epigenetic methylation signatures (Methylation, percentage, %)
大体时间：Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in depressive symptoms (scale score)
大体时间：Baseline to 6 and 12 months
Instrument: e.g., PHQ-9
Baseline to 6 and 12 months
Change in sleep quality (scale score)
大体时间：Baseline to 6 and 12 months
Instrument: e.g., PSQI
Baseline to 6 and 12 months
Change in quality of life (scale score)
大体时间：Baseline to 6 and 12 months
Instrument: e.g., EQ-5D or SF-36
Baseline to 6 and 12 months
Change in eating behavior (WREQ-C total and subscale scores)
大体时间：Baseline to 3, 6, and 12 months
Baseline to 3, 6, and 12 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Tri-Service General Hospital

合作者

National Science and Technology Council, Taiwan

调查人员

  • 研究主任：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.

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2026年3月31日

初级完成 (估计的)

2028年9月30日

研究完成 (估计的)

2029年9月30日

研究注册日期

首次提交

2026年5月1日

首先提交符合 QC 标准的

2026年5月10日

首次发布 (实际的)

2026年5月15日

研究记录更新

最后更新发布 (实际的)

2026年5月15日

上次提交的符合 QC 标准的更新

2026年5月10日

最后验证

2026年5月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • C202505161

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

IPD 计划说明

It is still ongoing and can not be shared before the final analysis.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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