About this trial
CARTIZ is a prospective observational clinical registry of adults in Mexico receiving tirzepatide (a dual GLP-1/GIP receptor agonist) under an independent clinical indication - typically type 2 diabetes, insulin resistance, obesity, renal protection, metabolic hypertension, or associated off-label metabolic use. The registry is entirely observational: CARTIZ does not initiate, modify, interrupt, or supply tirzepatide, and does not dictate dose, route, or duration. All pharmacological exposure decisions are made by the treating physician independently of study participation. The registry is operationalized through a four-institute architecture integrating three Mexican National Institutes of Health and one national imaging laboratory. Core 1 (Knee Cartilage Imaging, Ci3M UAM-Iztapalapa) performs bilateral 3T MRI with quantitative T2 mapping at Week 0 and Week 52. Core 2 (Cardiac Imaging, Instituto Nacional de Cardiología Ignacio Chávez) performs non-contrast cardiac computed tomography for radiomic phenotyping of epicardial adipose tissue at Week 0 and Week 52 under cardiovascular Co-Principal Investigator Dr. Erick Alexánderson Rosas. Core 3 (HLA Typing, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Transplant Department) performs Class I and Class II HLA typing by PCR-SSO Reverse Luminex. Core 4 (Body Composition, Universidad La Salle México) performs multi-frequency bioelectrical impedance analysis (seca mBCA) at six longitudinal timepoints capturing visceral adipose tissue trajectory, phase-angle trajectory, appendicular skeletal muscle mass, and hydration ratios at zero marginal cost. The registry enrolls n=30 patients across three clinical sites with identical protocol (IMSS Clínica Río Magdalena, INCMNSZ outpatient clinic, and a private practice site in Mexico City), generating 60 evaluable knees and 30 paired cardiac CT studies. The primary co-endpoints address a mechanistic question no other tirzepatide study is positioned to answer: whether the articular response to tirzepatide in inflammatory arthropathy precedes and mechanistically precedes weight loss, through formal mediation analysis of Week-4 ACR20 response via high-sensitivity C-reactive protein, SERPINB2, and dipeptidyl peptidase-4 activity, restricted to the Mechanistic Analysis Set of patients with tirzepatide exposure ≤16 weeks at Week 0 and delta-BMI \<1.0 kg/m² through Week 4. A prespecified Surgical Tissue Subcohort is declared at initial registration to establish public scientific priority on direct human epicardial adipose tissue transcriptomic characterization under dual GIP/GLP-1 receptor agonism. Subcohort participants who undergo clinically indicated cardiac surgery at INCar during follow-up (coronary artery bypass grafting, valve replacement, or combined procedures) are invited to provide specific additional informed consent for collection of epicardial adipose tissue fragments routinely excised during operative access and otherwise discarded as surgical waste. Operational launch is contingent on separate INCar tissue-specific approvals and will proceed via PRS record amendment when ready
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1. Age ≥18 years at the time of informed consent. 2. Currently receiving tirzepatide under an independent clinical indication (type 2 diabetes, insulin resistance, obesity with or without associated metabolic disease, renal protection, metabolic hypertension, or associated off-label metabolic use) prescribed by the treating physician independently of the registry.
Disqualifiers
1. Initiation or modification of a biologic disease-modifying antirheumatic drug (biologic DMARD) or JAK inhibitor within the 12 weeks prior to Week 0, or clinically anticipated initiation or modification during the first 12 weeks of follow-up. Washout may permit re-screening.
Trial population
Adults receiving tirzepatide under an independent clinical indication (type 2 diabetes, insulin resistance, obesity with or without associated metabolic disease, renal protection, metabolic hypertension, or off-label metabolic use) with current or historical documented musculoskeletal manifestation, enrolled across three clinical sites in Mexico City with identical protocol: IMSS Clínica Río Magdalena, INCMNSZ outpatient clinic, and a private practice site. The population is deliberately heterogeneous in tirzepatide indication and articular diagnosis to permit stratified analysis across the VAT-articular-cardiac-aging axis.
Trial design
Cohort
Prospective
Treatments tested in this trial
Tirzepatide
DrugDual GLP-1 and GIP receptor agonist administered subcutaneously at doses and intervals determined by the treating physician independently of this registry. The registry does not supply, initiate, modify, or discontinue tirzepatide; exposure is documented from the medical record and patient report.
Treatment groups
Trial outcomes
Primary outcomes
ACR20 response rate at Week 4 in the Mechanistic Analysis Set
Proportion of patients in the Mechanistic Analysis Set (tirzepatide exposure ≤16 weeks at Week 0 and delta-BMI \<1.0 kg/m² through Week 4) achieving ACR20 response (American College of Rheumatology 20% improvement criteria) at Week 4, assessed by standardized clinical evaluation.
Proportion of Week-4 ACR20 response mediated by biomarker panel in the Mechanistic Analysis Set
Proportion of the Week-4 ACR20 response mediated by the combined biomarker panel (high-sensitivity C-reactive protein, SERPINB2, dipeptidyl peptidase-4 activity) in the Mechanistic Analysis Set, assessed by the MacKinnon product-of-coefficients method with 10,000 bias-corrected and accelerated (BCa) bootstrap iterations. Decision thresholds are prespecified in the Statistical Analysis Plan.
Secondary outcomes
Change in knee cartilage T2 relaxation time from Week 0 to Week 52
Change in femoro-tibial and patellar cartilage T2 relaxation time from Week 0 to Week 52, bilateral knees, stratified by zone (medial femur, lateral femur, medial tibia, lateral tibia, patella), analyzed at Ci3M UAM-Iztapalapa on Philips 3T platform. Primary analysis: linear mixed-effects model with random intercepts for patient and for knee-within-patient.
Change in epicardial adipose tissue volume from Week 0 to Week 52
Change in epicardial adipose tissue (EAT) volume from Week 0 to Week 52 by non-contrast cardiac CT with prospective ECG gating at the Instituto Nacional de Cardiología Ignacio Chávez. Primary analysis: linear mixed-effects model adjusted for baseline EAT volume, age, sex, and baseline BMI. Unit of Measure: milliliters (mL)
Change in epicardial adipose tissue mean attenuation from Week 0 to Week 52
Change in epicardial adipose tissue (EAT) mean attenuation from Week 0 to Week 52 on the same non-contrast cardiac CT acquisitions at the Instituto Nacional de Cardiología Ignacio Chávez. Primary analysis: linear mixed-effects model adjusted for baseline EAT mean attenuation, age, sex, and baseline BMI. Units of Measure: Hounsfield units (HU)
Change in epicardial adipose tissue radiomic texture composite z-score from Week 0 to Week 52
Change in a prespecified compact radiomic signature derived from up to five IBSI-standardized texture features (first-order, GLCM, GLRLM, GLSZM, NGTDM families) computed on non-contrast cardiac CT EAT segmentations and expressed as a normalized composite z-score, from Week 0 to Week 52. Primary analysis: linear mixed-effects model adjusted for baseline composite z-score, age, sex, and baseline BMI. Units of Measure: z-score (dimensionless)
Sponsors and contacts
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JULIO GRANADOS MONTIEL
Lead sponsor
Universidad La Salle, Mexico
Sponsor institution
Instituto Nacional de Cardiologia Ignacio Chavez
Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborator
Metropolitan Autonomous University
Collaborator
Universidad Nacional Autonoma de Mexico
Collaborator
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