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
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Feng-Chih Kuo, M.D., Ph.D.
- Número de teléfono: 12687 886-2-87923311
- Correo electrónico: shoummie@hotmail.com
Ubicaciones de estudio
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Taipei, Taiwán, 114202
- Reclutamiento
- Tri-Service General Hospital
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Contacto:
- Feng-Chih Kuo, M.D., Ph.D.
- Número de teléfono: 12687 886-2-87923311
- Correo electrónico: shoummie@hotmail.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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).
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: 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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Comparador activo: 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Percent change in total body weight from baseline to 6 months.
Periodo de tiempo: 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.
Periodo de tiempo: 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.
Periodo de tiempo: Baseline to 6 months.
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Baseline to 6 months.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in waist circumference (cm)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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, %)
Periodo de tiempo: 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, %)
Periodo de tiempo: 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)
Periodo de tiempo: 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, %)
Periodo de tiempo: 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, %)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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, %)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: Baseline to 3, 6, and 12 months
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Baseline to 3, 6, and 12 months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Director de estudio: 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Trastornos Nutricionales
- Enfermedades metabólicas
- Sobrenutrición
- Peso corporal
- Trastornos del metabolismo de la glucosa
- Resistencia a la insulina
- Hiperinsulinismo
- Exceso de peso
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades Nutricionales y Metabólicas
- Signos y síntomas
- Obesidad
- Síndrome metabólico
- Aminoácidos, péptidos y proteínas
- Proteínas
- Receptor de péptido-1 tipo glucagón
- Receptores de péptidos tipo glucagón
- Receptores, acoplados a la proteína G
- Receptores, superficie celular
- Proteínas de membrana
- Receptores, hormona gastrointestinal
- Receptores, péptido
- Tirzepatide
- semaglutida
Otros números de identificación del estudio
- C202505161
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
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