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

10. maj 2026 opdateret af: 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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

120

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Taiwan
      • Taipei, Taiwan, 114202
        • Rekruttering
        • Tri-Service General Hospital
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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).

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Tirzepatide arm
starting at 2.5 mg weekly and escalated every month (5.0 mg, 7.5 mg to 10 mg) as tolerated
Medicin: 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.
Aktiv komparator: 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
Medicin: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Percent change in total body weight from baseline to 6 months.
Tidsramme: Baseline to 6 months
Baseline to 6 months
Total fat to lean mass loss ratio (DXA derived) from baseline to 6 months.
Tidsramme: Baseline to 6 months
Baseline to 6 months
Change in metabolic syndrome severity Z score from baseline to 6 months.
Tidsramme: Baseline to 6 months.
Baseline to 6 months.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in waist circumference (cm)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in waist-to-hip ratio (unitless ratio)
Tidsramme: Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in regional fat mass measured by DXA (grams)
Tidsramme: Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in regional lean mass measured by DXA (grams)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in 7-site skinfold thickness (mm)
Tidsramme: 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)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in abdominal visceral fat volume (mL)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in abdominal subcutaneous fat volume (mL)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in systolic and diastolic blood pressure (mmHg)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in fasting lipid profile (mg/dL)
Tidsramme: 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)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in hsCRP (mg/L)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in insulin sensitivity (HOMA-IR, unitless)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in β-cell function (HOMA-β, percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in AI-ECG predicted ASCVD risk score (percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in ECG-derived heart age (years)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in AI-ECG diabetes risk index (HbA1c, percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in estimated 10-year ASCVD risk (percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in bone mineral density (g/cm²)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in serum P1NP (ng/mL)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in serum CTX-1 (ng/mL)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in fasting plasma metabolomics profile (relative abundance units)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in fasting plasma proteomics profile (relative abundance units)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in microRNA expression signatures (normalized expression units)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in RNA-seq transcriptomic signatures (normalized counts, e.g., TPM)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in epigenetic methylation signatures (Methylation, percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in depressive symptoms (scale score)
Tidsramme: Baseline to 6 and 12 months
Instrument: e.g., PHQ-9
Baseline to 6 and 12 months
Change in sleep quality (scale score)
Tidsramme: Baseline to 6 and 12 months
Instrument: e.g., PSQI
Baseline to 6 and 12 months
Change in quality of life (scale score)
Tidsramme: 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)
Tidsramme: Baseline to 3, 6, and 12 months
Baseline to 3, 6, and 12 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Tri-Service General Hospital

Samarbejdspartnere

National Science and Technology Council, Taiwan

Efterforskere

  • Studieleder: 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.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

31. marts 2026

Primær færdiggørelse (Anslået)

30. september 2028

Studieafslutning (Anslået)

30. september 2029

Datoer for studieregistrering

Først indsendt

1. maj 2026

Først indsendt, der opfyldte QC-kriterier

10. maj 2026

Først opslået (Faktiske)

15. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

15. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

10. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • C202505161

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

IPD-planbeskrivelse

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

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