CARTIZ Registry: Cartilage, Arthropathy and Imaging Under Tirzepatide in Zone-stratified Cohorts - A Four-Institute Mexican Observational Registry

NCT07567378 | Not Yet Recruiting DMC

• 5 other identifiers: CARTIZ-2026-00164/019,13464/031,63564/039,91864/043,606
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Psoriatic Arthritis; Osteoarthitis; Knee; Diabetes (DM); Type 2 Diabetes Mellitus (T2DM); Obesity (Disorder); Insulin Resistance Syndrome; Metabolic Syndrome; Heart Failure; Preserved Ejection Fraction; Coronary Artery Disease; Atrial Fibrillation (AF); Non Alcholic Fatty Liver Disease; Sarcopenia; Pericardium

Keywords

Tirzepatide; Dual GIP/GLP-1 receptor agonist; Multi-nutrient-stimulated hormones; Psoriatic arthritis; Inflammatory arthropathy; ACR20; Cartilage T2 mapping; Quantitative knee MRI; Epicardial adipose tissue; Cardiac CT radiomics; Fat Attenuation Index; HLA typing; Visceral adipose tissue; Phase angle; seca mBCA; Bioelectrical impedance analysis; Mediation analysis; Weight-independent effect; Off-label exposure; Mexican registry; Epicardial adipose transcriptomics; Single-nucleus RNA sequencing

Outcome Measures

Primary Outcomes (2)

• 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.

  week 4

• 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.

  Week 4

Secondary Outcomes (12)

• Change in knee cartilage T2 relaxation time from Week 0 to Week 52

  Week 0 and week 52

• Change in epicardial adipose tissue volume from Week 0 to Week 52

  week 0 and week 52

• Change in epicardial adipose tissue mean attenuation from Week 0 to Week 52

  week 0 and week 52

• Change in epicardial adipose tissue radiomic texture composite z-score from Week 0 to Week 52

  week 0 and week 52

• Longitudinal visceral adipose tissue trajectory over six timepoints

  week 0 through week 52

Study Arms (3)

Retrospective-Prospective

Patients currently under the Principal Investigator's care who are already receiving tirzepatide for an independent clinical indication at the time of registry enrolment, with pre-tirzepatide articular, metabolic, and clinical documentation available in the medical record. Baseline pre-tirzepatide state is reconstructed retrospectively from structured medical record review under a specific informed consent attestation; Week-0 biospecimen and imaging acquisition is prospective. Expected n=10-20 from the Principal Investigator's existing patient pool. Recruitment Status: Not yet recruiting.

Drug: Tirzepatide

Fully Prospective

Patients identified across the three clinical sites (IMSS Clínica Río Magdalena, INCMNSZ outpatient clinic, private practice in Mexico City) who are initiating tirzepatide under an independent clinical indication during the registry enrolment window, enrolled at or before Week 0 of tirzepatide exposure. Protocol is identical to Cohort 1 from Week 0 forward; the difference is the absence of pre-tirzepatide retrospective reconstruction. Expected n=10-20 recruited over 6-12 months. Recruitment Status: Not yet recruiting.

Drug: Tirzepatide

Surgical Tissue Subcohort

Subset of enrolled Cohort 1 or Cohort 2 participants undergoing clinically indicated cardiac surgery at the Instituto Nacional de Cardiología Ignacio Chávez during follow-up (coronary artery bypass grafting, valve replacement, or combined procedures), providing additional informed consent for intraoperative collection of epicardial adipose tissue fragments routinely excised during cardiac access and discarded as surgical waste. Tissue acquisition does not modify the surgical procedure. This subcohort is declared at initial registration to establish scientific priority on direct human epicardial adipose tissue transcriptomic characterization under dual GIP/GLP-1 receptor agonism. Operational launch requires (a) favorable opinion of INCar Comité de Investigación and Comité de Ética en Investigación for the tissue-specific protocol, (b) formal agreement with INCar Servicio de Cirugía Cardiovascular, (c) PRS amendment reflecting operational launch. Recruitment Status: Not yet recruiting.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Dual 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.

Fully Prospective; Retrospective-Prospective; Surgical Tissue Subcohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• \. 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.
• \. Presence of at least one objectively documented musculoskeletal manifestation - current or historical - defined as any of: (i) inflammatory arthralgia affecting one or more joints with clinical, imaging, or serological support; (ii) CASPAR-positive psoriatic arthritis; (iii) radiographically documented knee osteoarthritis; (iv) enthesitis on physical examination or ultrasound; (v) documented inflammatory arthropathy of the spine or peripheral joints with a specialist diagnosis.
• \. For the retrospective-prospective component: availability of clinical documentation of articular state prior to tirzepatide initiation in the patient's medical record. Documentation may include physical examination notes, imaging, laboratory values, or specialist consultation notes.
• \. Signed informed consent for registry enrolment, longitudinal serum biobanking, HLA typing at INCMNSZ, quantitative knee MRI with T2 mapping at Ci3M UAM-Iztapalapa at Week 0 and Week 52, non-contrast cardiac CT at INCar at Week 0 and Week 52, multi-frequency bioelectrical impedance analysis at Universidad La Salle México at six timepoints, and (where applicable) medical record review. Each attestation is consented modularly within a single document.
• \. Clinical plan to continue tirzepatide for at least 52 weeks from registry Week 0, based on the treating physician's evaluation of current clinical indication. Discontinuation during follow-up is captured as an outcome variable and does not remove the patient from the registry.
• For the Surgical Tissue Subcohort (Cohort 3) only - additional criteria applied at the time of subcohort enrolment:
• s. Scheduled clinically indicated cardiac surgery at the Instituto Nacional de Cardiología Ignacio Chávez (coronary artery bypass grafting, valve replacement, or combined procedures) during registry follow-up.
• s. Specific additional informed consent for intraoperative collection of epicardial adipose tissue fragments.

You may not qualify if:

• \. 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.
• \. Major joint surgery within the 3 months prior to Week 0, or planned major joint surgery within the 12 months following Week 0, involving any joint scheduled for evaluation in the registry.
• \. Intra-articular corticosteroid or hyaluronic acid injection within the 6 weeks prior to baseline biospecimen collection in any joint. Patients beyond the 6-week washout are eligible.
• \. Active malignancy, with the exception of adequately treated non-melanoma skin carcinoma. History of malignancy in remission ≥5 years is permitted at the discretion of the treating investigator.
• \. Current pregnancy, lactation, or planned pregnancy within the 12-month observation period.
• \. Absolute contraindication to MRI, including non-MRI-compatible cardiac pacemaker or implanted defibrillator, ferromagnetic intracranial vascular clips, non-documented non-MRI-compatible cochlear implants, or other contraindication per the local MRI safety protocol.
• \. Systemic rheumatologic disease other than psoriatic arthritis or osteoarthritis requiring active immunomodulation, specifically: seropositive rheumatoid arthritis on biologic therapy, active systemic lupus erythematosus on immunomodulation, active vasculitis on immunosuppression, or other systemic disease whose treatment confounds the inflammatory axis the registry is designed to characterize.
• \. Inability to provide informed consent (cognitive impairment, language barrier not resolvable with site interpreter, or other incapacity to understand the protocol), or anticipated inability to complete the 52-week follow-up.
• s. Prior major cardiac surgery resulting in extensive pericardial adhesions that preclude safe intraoperative EAT fragment collection, as assessed by the operating cardiac surgeon.
• s. Emergency cardiac surgery precluding the specific informed consent process.

Sponsors & Collaborators

• JULIO GRANADOS MONTIEL: lead
• Instituto Nacional de Cardiologia Ignacio Chavez: collaborator
• Instituto Mexicano del Seguro Social: collaborator
• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: collaborator
• Universidad Autonoma Metropolitana - Unidad Lerma: collaborator

Study Sites (1)

IMSS Clínica Río Magdalena

Mexico City, Mexico City, 01090, Mexico

Location

Related Publications (13)

• Granados-Montiel J, et al. SERPINB2 as a chondrogenic lineage marker. bioRxiv 2026. doi:10.64898/2026.03.29.713197

  RESULT

• Yu J, Hou M, Deng Y, et al. Double-Pronged NAD Preservation: Delaying Cellular Senescence and Initiating Musculoskeletal Regeneration. Aging Cell. 2026;25:e70468.

  RESULT

• Zwanenburg A, Vallieres M, Abdalah MA, Aerts HJWL, Andrearczyk V, Apte A, Ashrafinia S, Bakas S, Beukinga RJ, Boellaard R, Bogowicz M, Boldrini L, Buvat I, Cook GJR, Davatzikos C, Depeursinge A, Desseroit MC, Dinapoli N, Dinh CV, Echegaray S, El Naqa I, Fedorov AY, Gatta R, Gillies RJ, Goh V, Gotz M, Guckenberger M, Ha SM, Hatt M, Isensee F, Lambin P, Leger S, Leijenaar RTH, Lenkowicz J, Lippert F, Losnegard A, Maier-Hein KH, Morin O, Muller H, Napel S, Nioche C, Orlhac F, Pati S, Pfaehler EAG, Rahmim A, Rao AUK, Scherer J, Siddique MM, Sijtsema NM, Socarras Fernandez J, Spezi E, Steenbakkers RJHM, Tanadini-Lang S, Thorwarth D, Troost EGC, Upadhaya T, Valentini V, van Dijk LV, van Griethuysen J, van Velden FHP, Whybra P, Richter C, Lock S. The Image Biomarker Standardization Initiative: Standardized Quantitative Radiomics for High-Throughput Image-based Phenotyping. Radiology. 2020 May;295(2):328-338. doi: 10.1148/radiol.2020191145. Epub 2020 Mar 10.

  PMID: 32154773 RESULT

• Oikonomou EK, Marwan M, Desai MY, et al. Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study). Lancet. 2018;392:929-939.

  RESULT

• Antonopoulos AS, Sanna F, Sabharwal N, Thomas S, Oikonomou EK, Herdman L, Margaritis M, Shirodaria C, Kampoli AM, Akoumianakis I, Petrou M, Sayeed R, Krasopoulos G, Psarros C, Ciccone P, Brophy CM, Digby J, Kelion A, Uberoi R, Anthony S, Alexopoulos N, Tousoulis D, Achenbach S, Neubauer S, Channon KM, Antoniades C. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med. 2017 Jul 12;9(398):eaal2658. doi: 10.1126/scitranslmed.aal2658.

  PMID: 28701474 RESULT

• Qin H, Yu J, Yu H, Zhou C, Yuan D, Wang Z, Zhu Z, Wei G, Ou P, Li Z, Jiang H, Shen J, Xiao G, Bai X, Wang H, Zhang HT, Speakman JR, Chen D, Tong L. Semaglutide ameliorates osteoarthritis progression through a weight loss-independent metabolic restoration mechanism. Cell Metab. 2026 Mar 3;38(3):582-597.e6. doi: 10.1016/j.cmet.2026.01.008. Epub 2026 Feb 9.

  PMID: 41666927 RESULT

• Regmi A, Aihara E, Christe ME, Varga G, Beyer TP, Ruan X, Beebe E, O'Farrell LS, Bellinger MA, Austin AK, Lin Y, Hu H, Konkol DL, Wojnicki S, Holland AK, Friedrich JL, Brown RA, Estelle AS, Badger HS, Gaidosh GS, Kooijman S, Rensen PCN, Coskun T, Thomas MK, Roell W. Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor. Cell Metab. 2024 Jul 2;36(7):1534-1549.e7. doi: 10.1016/j.cmet.2024.05.010. Epub 2024 Jun 14.

  PMID: 38878772 RESULT

• Merola JF, Mease P, Kivitz A, Sattar N, Coates LC, Aletaha D, Kartman CE, Fischer P, Sun L, Martinez-Osuna P, Kronbergs A, Prajapati P, Cardoso A, Genovese MC, Ogdie A. Ixekizumab With Tirzepatide Achieved Greater Disease Control Than Ixekizumab Alone in Adults With Psoriatic Arthritis and Overweight or Obesity: Results From a Randomized Clinical Trial. Arthritis Rheumatol. 2026 Mar 28. doi: 10.1002/art.70134. Online ahead of print.

  PMID: 41903163 RESULT

• Meyhöfer, S.M., Cariou, B., Cercato, C. et al. Semaglutide on liver fibrosis and heart outcomes in patients at high risk of liver fibrosis: a prespecified analysis of the SELECT randomized trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04281-1

  RESULT

• Nicholls SJ, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes (SURPASS-CVOT). N Engl J Med. 2025;393:2409-2420.

  RESULT

• Packer M, Zile MR, Kramer CM, DiMaria JM, Baum SJ, Litwin SE, Murakami M, Zhou C, Ou Y, Koeneman L, Borlaug BA; SUMMIT Trial Study Group. Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis. J Am Coll Cardiol. 2025 Sep 9;86(10):696-707. doi: 10.1016/j.jacc.2025.06.058.

  PMID: 40903131 RESULT

• Kang, Y.M., Harrington, J., Aroda, V.R. et al. Beyond GLP1: modulating multiple nutrient-stimulated hormone pathways to reduce cardiovascular risk. Nat Rev Cardiol (2026). https://doi.org/10.1038/s41569-026-01296-6

  RESULT

• Kramer CM, Borlaug BA, Zile MR, Ruff D, DiMaria JM, Menon V, Ou Y, Zarante AM, Hurt KC, Murakami M, Packer M; SUMMIT Trial Study Group. Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy. J Am Coll Cardiol. 2025 Feb 25;85(7):699-706. doi: 10.1016/j.jacc.2024.11.001. Epub 2024 Nov 18.

  PMID: 39566869 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Longitudinal serum biobanking at six timepoints (Week 0, 2, 4, 12, 24, 52), minimum four 500 µL aliquots per visit, processed under standardized SOP and archived in a centralized biobank; whole blood for HLA Class I and Class II typing (PCR-SSO Reverse Luminex, INCMNSZ Transplant Department). In the prespecified Surgical Tissue Subcohort (Not Yet Recruiting at initial registration), epicardial adipose tissue fragments obtained intraoperatively during clinically indicated cardiac surgery (coronary artery bypass grafting, valve replacement, or combined procedures) that would otherwise be discarded as surgical waste, preserved as fresh-frozen aliquots (RNAlater, OCT) and formalin-fixed aliquots (10% neutral-buffered formalin) for bulk and/or single-nucleus RNA sequencing, histological characterization, and biobanking.

MeSH Terms

Conditions

Arthritis, Psoriatic; Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity; Metabolic Syndrome; Heart Failure; Coronary Artery Disease; Atrial Fibrillation; Sarcopenia

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Heart Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Julio Granados-Montiel, MD, PhD

  Universidad La Salle

  PRINCIPAL INVESTIGATOR

• Erick Alexánderson-Rosas, MD

  Instituto Nacional de Cardiología Ignacio Chávez

  PRINCIPAL INVESTIGATOR

• Marwin Gutierrez, MD

  Centro de Enfermedades Reumaticas y Musculoesqueléticas

  PRINCIPAL INVESTIGATOR

• Mario Vilatoba, MD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  PRINCIPAL INVESTIGATOR

• Jorge Aspiroz-Leehan, PhD

  Metropolitan Autonomous University

  PRINCIPAL INVESTIGATOR

• Rodrigo Morales-Guadarrama, PhD

  Metropolitan Autonomous University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julio Granados-Montiel, MD, PhD

CONTACT

+52 5554329237; juliogram@gmail.com

Marwin Gutiérrez, MD

CONTACT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 52 Weeks
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Investigador en Ciencias Médicas

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: May 5, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): May 1, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: From approximately 6 months after primary publication, under the access tiers defined in the Sponsor Access Framework. T1 discussions may begin at any time under Mutual Non-Disclosure Agreement
• Access Criteria: Access is governed by the Sponsor Access Framework v2.0 of the CARTIZ registry. Pharmaceutical, diagnostic, and academic requesters are eligible under the framework's tiered instruments. Initial inquiries are directed to the Principal Investigator (contact details in Module 10). T2 access requires an executed Material Transfer Agreement and Data Use Agreement. T3 and T4 access require commercial terms and Independent Scientific Advisory Board consultation.

Locations

ME (1)