Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-03-30 @ 1:27 AM
Study NCT ID:
NCT07444203
Status:
RECRUITING
Last Update Posted:
2026-03-02
First Post:
2026-02-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Transformative Research in Diabetic Nephropathy 2.0
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003928', 'term': 'Diabetic Nephropathies'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D051436', 'term': 'Renal Insufficiency, Chronic'}, {'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}], 'ancestors': [{'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D048909', 'term': 'Diabetes Complications'}, {'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077203', 'term': 'Sodium-Glucose Transporter 2 Inhibitors'}, {'id': 'D000097789', 'term': 'Glucagon-Like Peptide-1 Receptor Agonists'}, {'id': 'D000451', 'term': 'Mineralocorticoid Receptor Antagonists'}], 'ancestors': [{'id': 'D045504', 'term': 'Molecular Mechanisms of Pharmacological Action'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}, {'id': 'D007004', 'term': 'Hypoglycemic Agents'}, {'id': 'D045505', 'term': 'Physiological Effects of Drugs'}, {'id': 'D006727', 'term': 'Hormone Antagonists'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D062865', 'term': 'Diuretics, Potassium Sparing'}, {'id': 'D004232', 'term': 'Diuretics'}, {'id': 'D045283', 'term': 'Natriuretic Agents'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Whole blood, Urine, and Kidney tissue specimen.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-11-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2028-11-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-24', 'studyFirstSubmitDate': '2026-02-24', 'studyFirstSubmitQcDate': '2026-02-24', 'lastUpdatePostDateStruct': {'date': '2026-03-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-05-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in Kidney Tissue molecular fingerprint', 'timeFrame': 'Baseline enrollment to 18 months.', 'description': 'Change/differences in kidney tissue molecular "fingerprint" (molecular pathways / spatial gene expression signatures derived from archived kidney tissue) comparing participants exposed to sodium-glucose cotransporter 2 inhibitors versus controls and participants on other therapies. Tissue profiling includes single-cell spatial transcriptomics with differential expression and pathway analyses stratified by therapy exposure.'}], 'secondaryOutcomes': [{'measure': 'Change in estimated glomerular filtration rate (eGFR)', 'timeFrame': 'Baseline to 18 months', 'description': 'Change in eGFR calculated using the 2021 race-free CKD-EPI equation.'}, {'measure': 'Change in urine protein/creatinine ratio', 'timeFrame': 'Baseline to 6 months.', 'description': 'Change in urine protein/creatinine ratio over follow-up.'}, {'measure': 'Descriptive histopathology features and spatial gene expression patterns across cohorts', 'timeFrame': 'At enrollment/baseline (Single assessment on the archived clinical specimen slide)', 'description': 'Descriptive histopathological features (fibrosis, sclerosis, inflammation, vascular changes) and spatial gene expression patterns evaluated across diabetic kidney disease, disease controls, donor, and nephrectomy cohorts.'}, {'measure': 'Associations between histopathological features and clinical outcomes', 'timeFrame': 'Up to 3 years (longitudinal outcome abstraction, including dialysis/transplant/kidney failure/mortality as captured).', 'description': 'Associations between histopathological features and clinical outcomes including eGFR slope, proteinuria, kidney failure, and transplant.'}, {'measure': 'Associations between histopathological features and prior medication exposures', 'timeFrame': 'Baseline (prior/current medication exposure history at enrollment).', 'description': 'Associations between histopathological features and prior medication exposures, including SGLT2 inhibitors, renin-angiotensin-aldosterone system blockade, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and other therapies.'}, {'measure': 'Feasibility metrics', 'timeFrame': 'During study accrual and specimen acquisition (up to 3 years).', 'description': 'Accrual rate by cohort, proportion of slides successfully retrieved, and slide quality metrics.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Diabetic nephropathy', 'Chronic kidney disease', 'Diabetic kidney disease', 'Sodium-glucose cotransporter 2 inhibitors', 'Spatial transcriptomics', 'Kidney-protective therapy'], 'conditions': ['Diabetic Nephropathies', 'Kidney Diseases', 'Renal Insufficiency, Chronic', 'Diabetes Mellitus, Type 2']}, 'descriptionModule': {'briefSummary': 'The goal of this observational study is to learn more about kidney health in adults with diabetic kidney disease and other groups. Researchers will study kidney tissue and other samples. They want to learn how sodium-glucose cotransporter-2 (SGLT2) inhibitors, a type of diabetes medicine, may affect the kidneys. People can join only if they are already having a kidney biopsy or kidney surgery as part of their regular medical care.\n\nThe main questions this study aims to answer are:\n\n* Do people who take SGLT2 inhibitors show different biological patterns in kidney tissue than similar people who do not take them?\n* Are these kidney tissue patterns linked with how kidney health changes over time?\n\nResearchers will compare participants who take SGLT2 inhibitors with similar participants who do not take these medicines.\n\nParticipants will:\n\nLet researchers use one stored slide of kidney tissue from their regular care (no extra research biopsy) Give a blood sample and a urine sample Let researchers review medical record information over time', 'detailedDescription': 'TRIDENT 2.0 is a multicenter observational translational study that characterizes kidney molecular and histopathologic features in relation to exposure to kidney-protective therapies, with a focus on sodium-glucose cotransporter-2 (SGLT2) inhibitors. The study leverages archived clinical kidney pathology material and harmonized clinical data to support integrated molecular-histologic analyses across participating sites.\n\nTissue sources and central repository workflows:\n\nFormalin-fixed, paraffin-embedded (FFPE) kidney tissue sections/slides are generated from archived clinical pathology material (including clinically indicated kidney biopsies and available donor or nephrectomy specimens) and transferred under coded identifiers to a central repository for downstream molecular assays and digital pathology.\n\nSpatial transcriptomics and molecular profiling:\n\nSpatially resolved transcriptomic methods are used to generate high-resolution molecular maps while preserving tissue architecture. FFPE (or fresh-frozen, when available) sections may be processed using commercially available spatial transcriptomics platforms (e.g., 10x Genomics Visium, NanoString CosMx, Xenium) or updated technologies implemented under study governance. Standard quality control procedures evaluate tissue integrity, RNA quality, capture efficiency, and resolution of major kidney compartments and cell types. Sequencing is performed on Illumina platforms with platform-appropriate depth, followed by preprocessing using platform-specific pipelines and downstream analysis in R/Python workflows (e.g., Seurat or equivalent) with normalization and batch correction as needed. Planned analyses include identification of cell-type and sub-cell-type signatures in spatial context, mapping of injury patterns (e.g., fibrosis/inflammation/vascular remodeling), and comparative molecular profiling across disease categories and therapy exposure groups with adjustment for relevant covariates.\n\nDigital pathology and centralized histopathology review:\n\nDigitized clinical stains and available diagnostic images are used for centralized review and standardized lesion scoring by renal pathologists. When applicable, diabetic kidney disease (DKD) is classified using established renal pathology criteria. Specimen adequacy metrics are used to guide analytic inclusion and sensitivity analyses.\n\nLinked clinical data (high level):\n\nClinical data are harmonized across sites to support clinicopathologic and molecular integration, including medication exposure history and relevant laboratory and diagnostic variables. Longitudinal clinical information is used to contextualize molecular and histologic findings for downstream modeling.\n\nStatistical and integrative analytic approach:\n\nAnalytic methods include differential expression and pathway analyses with appropriate multiple-testing control and covariate adjustment. Integrative modeling may combine molecular, histologic, and clinical domains using dimension reduction and regularized approaches to derive molecular signatures associated with disease state and therapy exposure.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'TRIDENT 2.0 will enroll approximately 200 participants across multiple sites. Eligible participants include:\n\n* Patients with diabetic kidney disease (DKD) confirmed by clinically indicated biopsy.\n* Patients with other kidney diseases (disease controls).\n* Living kidney donors (donor biopsy tissue).\n* Patients undergoing nephrectomy (non-tumor, adjacent normal tissue when available).\n\nAll participants must provide informed consent for release of one H\\&E slide from their clinical biopsy or surgical specimen and for abstraction of relevant clinical data.', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥18 years\n* eGFR ≥10 ml/min/1.73 m2 based on the 2021 race-free CKD-EPI equation13\n* Underwent a clinically indicated kidney biopsy, living donor biopsy, or nephrectomy (non-tumor adjacent tissue available).\n* Able and willing to provide informed consent for release of one pathology and clinical data abstraction.\n\nExclusion Criteria:\n\n* Inability to provide informed consent.\n* Archived biopsy or surgical tissue unavailable for slide preparation.\n* Any local institutional policy that prohibits release of H\\&E slides for research.'}, 'identificationModule': {'nctId': 'NCT07444203', 'acronym': 'TRIDENT 2', 'briefTitle': 'Transformative Research in Diabetic Nephropathy 2.0', 'organization': {'class': 'OTHER', 'fullName': 'University of Pennsylvania'}, 'officialTitle': 'Transformative Research in Diabetic Nephropathy 2.0: A Proof of Principle Study of SGLT2 Inhibitors (TRIDENT 2.0)', 'orgStudyIdInfo': {'id': '849580'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Biopsy-confirmed Diabetic Kidney Disease Cohort', 'description': 'Adults with diabetic kidney disease confirmed by a clinically indicated kidney biopsy. This cohort is used to evaluate kidney molecular and histopathologic features in relation to medication exposure history.\n\nInterventions/exposures of interest (observational): Primary exposure is sodium-glucose cotransporter 2 inhibitors; additional therapy exposures of interest include renin-angiotensin-aldosterone system blockade, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and other therapies.', 'interventionNames': ['Drug: Sodium-glucose cotransporter 2 inhibitors (SGLT2i)', 'Drug: Renin-angiotensin-aldosterone system blockade', 'Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA)', 'Drug: Mineralocorticoid Receptor Antagonists(MRAs)']}, {'label': 'Disease Control Kidney Disease Cohort', 'description': 'Adults with other forms of kidney disease (non-DKD), included as disease controls for cross-disease comparisons of molecular and histologic patterns.\n\nInterventions/exposures of interest (observational): Medication exposure history is captured to support comparisons across therapy classes, including SGLT2 inhibitors and other disease-modifying therapies.', 'interventionNames': ['Drug: Sodium-glucose cotransporter 2 inhibitors (SGLT2i)', 'Drug: Renin-angiotensin-aldosterone system blockade', 'Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA)', 'Drug: Mineralocorticoid Receptor Antagonists(MRAs)']}, {'label': 'Living Kidney Donor Cohort', 'description': 'Living kidney donors with available donor biopsy tissue, included as a comparator group to provide reference kidney tissue profiles.\n\nInterventions/exposures of interest (observational): Medication exposure history (including kidney-protective therapies where applicable) may be used in descriptive and comparative analyses; donors primarily serve as a reference/control tissue cohort.', 'interventionNames': ['Drug: Sodium-glucose cotransporter 2 inhibitors (SGLT2i)', 'Drug: Renin-angiotensin-aldosterone system blockade', 'Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA)', 'Drug: Mineralocorticoid Receptor Antagonists(MRAs)']}, {'label': 'Nephrectomy Control Cohort', 'description': 'Adults undergoing nephrectomy with non-tumor, adjacent normal kidney tissue available, included as a control/reference tissue cohort.\n\nInterventions/exposures of interest (observational): Medication exposure history (including SGLT2 inhibitors and other kidney-protective therapies) may be incorporated in comparative analyses across cohorts.', 'interventionNames': ['Drug: Sodium-glucose cotransporter 2 inhibitors (SGLT2i)', 'Drug: Renin-angiotensin-aldosterone system blockade', 'Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA)', 'Drug: Mineralocorticoid Receptor Antagonists(MRAs)']}], 'interventions': [{'name': 'Sodium-glucose cotransporter 2 inhibitors (SGLT2i)', 'type': 'DRUG', 'otherNames': ['SGLT2 inhibitors'], 'description': 'Standard-of-care exposure to sodium-glucose cotransporter 2 inhibitors documented from medication history. Participants are not assigned therapy. Exposure status is used for observational comparisons of kidney tissue molecular and histopathologic features.', 'armGroupLabels': ['Biopsy-confirmed Diabetic Kidney Disease Cohort', 'Disease Control Kidney Disease Cohort', 'Living Kidney Donor Cohort', 'Nephrectomy Control Cohort']}, {'name': 'Renin-angiotensin-aldosterone system blockade', 'type': 'DRUG', 'description': 'Standard-of-care exposure to renin-angiotensin-aldosterone system blockade documented from medication history for observational comparisons.', 'armGroupLabels': ['Biopsy-confirmed Diabetic Kidney Disease Cohort', 'Disease Control Kidney Disease Cohort', 'Living Kidney Donor Cohort', 'Nephrectomy Control Cohort']}, {'name': 'Glucagon-like peptide-1 receptor agonists (GLP 1 RA)', 'type': 'DRUG', 'otherNames': ['GLP-1 receptor agonists'], 'description': 'Standard-of-care exposure documented from medication history for observational comparisons.', 'armGroupLabels': ['Biopsy-confirmed Diabetic Kidney Disease Cohort', 'Disease Control Kidney Disease Cohort', 'Living Kidney Donor Cohort', 'Nephrectomy Control Cohort']}, {'name': 'Mineralocorticoid Receptor Antagonists(MRAs)', 'type': 'DRUG', 'otherNames': ['MRAs'], 'description': 'Standard-of-care exposure documented from medication history for observational comparisons.', 'armGroupLabels': ['Biopsy-confirmed Diabetic Kidney Disease Cohort', 'Disease Control Kidney Disease Cohort', 'Living Kidney Donor Cohort', 'Nephrectomy Control Cohort']}]}, 'contactsLocationsModule': {'locations': [{'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Gaia Coppock, MD', 'role': 'CONTACT', 'email': 'Gaia.Coppock@pennmedicine.upenn.edu', 'phone': '2673030158'}, {'name': 'Mohammed Al Dulaimee, BS', 'role': 'CONTACT', 'email': 'mohammed.aldulaimee@pennmedicine.upenn.edu', 'phone': '5853589733'}], 'facility': 'Penn Presbyterian Medical Center', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}], 'centralContacts': [{'name': 'Gaia Coppock, MD', 'role': 'CONTACT', 'email': 'Gaia.Coppock@pennmedicine.upenn.edu', 'phone': '2673030158'}, {'name': 'Mohammed Al Dulaimee, BS', 'role': 'CONTACT', 'email': 'mohammed.aldulaimee@pennmedicine.upenn.edu', 'phone': '5853589733'}], 'overallOfficials': [{'name': 'Katalin Susztak, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Pennsylvania'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Pennsylvania', 'class': 'OTHER'}, 'collaborators': [{'name': 'GlaxoSmithKline', 'class': 'INDUSTRY'}, {'name': 'Boehringer Ingelheim', 'class': 'INDUSTRY'}, {'name': 'Regeneron Pharmaceuticals', 'class': 'INDUSTRY'}, {'name': 'Novo Nordisk A/S', 'class': 'INDUSTRY'}, {'name': 'AstraZeneca', 'class': 'INDUSTRY'}, {'name': 'Genentech, Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD, PhD', 'investigatorFullName': 'Katalin Susztak', 'investigatorAffiliation': 'University of Pennsylvania'}}}}