Ignite Creation Date:
2025-12-24 @ 9:37 PM
Ignite Modification Date:
2025-12-29 @ 4:07 AM
Study NCT ID:
NCT06147232
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-01-27
First Post:
2023-11-19
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Prevention of Chronic Kidney Disease(CDK) Progression in Type 1 Diabetes With Long Term Use of Sodium-Glucose-coTransporter Inhibitors Avoiding Kidney hypOxia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D003928', 'term': 'Diabetic Nephropathies'}, {'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}, {'id': 'D000419', 'term': 'Albuminuria'}, {'id': 'D000860', 'term': 'Hypoxia'}], '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': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D011507', 'term': 'Proteinuria'}, {'id': 'D014555', 'term': 'Urination Disorders'}, {'id': 'D020924', 'term': 'Urological Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012818', 'term': 'Signs and Symptoms, Respiratory'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C575681', 'term': '(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'randomized, double-blinded, placebo-controlled, cross-over intervention study'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 69}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-02', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2027-05', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-01-22', 'studyFirstSubmitDate': '2023-11-19', 'studyFirstSubmitQcDate': '2023-11-19', 'lastUpdatePostDateStruct': {'date': '2025-01-27', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-11-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-05', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Ethnicity', 'timeFrame': 'From baseline to 30 weeks.', 'description': 'if African-Caribbean ethnicity is associated with any of the above secondary outcomes or baseline differences in cardio-renal disease markers/imaging measures'}], 'primaryOutcomes': [{'measure': 'Change in dynamic R2*-weighted signal (BOLD) as an indirect measure of renal blood oxygenation', 'timeFrame': '0 to 12 weeks in both treatment arms, last measure 30 weeks after randomization.', 'description': 'difference between change from 0 to 12 weeks after treatment with sotagliflozin compared to treatment with placebo'}], 'secondaryOutcomes': [{'measure': 'Change in renal perfusion (medullary and cortical)', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization', 'description': 'Measured with MRI by arterial spin labelling in mL/g/min'}, {'measure': 'Change in renal artery flow', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization', 'description': 'Renal artery flow measured by using phase contrast (PC) MRI. It is measured in mL/min.'}, {'measure': 'Change in renal oxygen consumption', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization', 'description': 'Renal oxygen consumption measured by MRI with T2-relaxation-under-spin-tagging.'}, {'measure': 'Change in renal parenchymal triglyceride fraction', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization', 'description': 'Renal parenchymal triglyceride fraction is measured by MRI spectroscopy'}, {'measure': 'Change in renal fibrosis', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization', 'description': 'Renal fibrosis is measured by MRI-derived apparent diffusion coefficient'}, {'measure': 'Change in left ventricular ejection fraction', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization', 'description': 'Left ventricular ejection fraction is assessed by MRI'}, {'measure': 'Change in albuminuria', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.', 'description': 'Urinary albumin-creatinine ratio (UACR) - morning void spot urine samples collected at home by participants.'}, {'measure': 'Change in levels of ketone bodies', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.', 'description': 'Capillary blood ketones, possibly measured by continous ketone monitoring device'}, {'measure': 'Change in plasma and urine inflammation- and fibrosis biomarkers', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.', 'description': 'Measured from blood and urine samples using a commercially available panel from the company Olink. Includes 92 biomarkers.'}, {'measure': 'Change in endogenous erythropoietin', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.', 'description': 'Analysis on blood samples at regional hospital laboratory.'}, {'measure': 'Change in pro brain natriuretic peptide', 'timeFrame': 'From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.', 'description': 'Analysis on blood samples at regional hospital laboratory.'}, {'measure': 'Difference in Kidney Function after 12 weeks treatment with sotagliflozin vs placebo', 'timeFrame': 'From 12 to 30 weeks after randomization', 'description': 'Glomerular filtration rate. At Steno Diabetes Center Copenhagen this will be measured by plasma clearance of Tc-99m diethylene-triamine-pentaacetate.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Nephropathy', 'Diabetic Nephropathies', 'Diabetes Mellitus, Type 1', 'Albuminuria', 'Diabetic Complications Renal', 'Diabetic Complications Cardiovascular', 'Hypoxia']}, 'descriptionModule': {'briefSummary': "Background: Sodium-glucose-cotransporter (SGLT) inhibition has been observed to reduce risk of cardiovascular events and kidney failure in persons with type 2 diabetes. People with type 1 diabetes also have increased risk of cardiovascular and kidney disease, and may benefit from SGLT-inhibition. The exact mechanism of how SGLT-inhibition benefits the kidneys are yet unknown. Change in renal hypoxia may be a factor.\n\nObjective: The primary aim of this study is to assess the effects of 12 weeks SGLT-1 and 2 inhibition on renal oxygenation in persons with type 1 diabetes and chronic kidney disease.\n\nFurther aims are to study if renal oxygen consumption and response to SGLT-inhibition differs between people of African-Caribbean or Northern European decent.\n\nAdditionally effects on left ventricular ejection fraction, kidney function and biomarkers in blood and urine will be explored.\n\nMethod: 12 weeks treatment with oral sotagliflozin or matching placebo as intervention. Kidney oxygenation and perfusion parameters and left ventricular ejection fraction will be assessed by functional magnetic resonance imaging. Kidney function and biomarkers will be assessed according to local hospital laboratory guidelines.\n\nDesign: Randomized, double-blinded, placebo-controlled, cross over intervention study.\n\nStudy population: 69 persons with type 1 diabetes and diabetic kidney disease with albuminuria will be included, 39 at Steno Diabetes Center Copenhagen, 30 at King's College London.\n\nEndpoints: Primary end-point: Change from 0 to 12 weeks in dynamic R2\\*-weighted signal after treatment with sotagliflozin compared to placebo. Secondary endpoints: Change from 0 to 12 weeks with sotagliflozin compared with placebo on renal perfusion, renal artery flow, renal oxygen consumption, renal parenchymal triglyceride fraction, renal fibrosis, left ventricular ejection fraction, urinary albumin-creatinin ratio, ketone bodies, erythropoietin, pro brain natriuretic peptide, and plasma- and urine inflammation- and fibrosis biomarkers as well as difference after 12 weeks treatment in glomerular filtration rate.\n\nTimeframe: Inclusion of patients from february 2024. Last visit september 2025. Presentation spring 2026, publication fall 2026."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Persons ≥ 18 years of age with a diagnosis of type 1 diabetes (age at onset \\<40 years; permanent insulin treatment initiated within 1 year of diagnosis)\n2. Albuminuria: UACR \\> 100 mg/g (in ≥2 out 3 morning spot urine collections prior to randomization)\n3. estimated Glomerular Filtration Rate(eGFR) ≥25 and \\< 75 ml/min/1.73m2\n4. Participants must be on stable renin-angiotensin system blocking treatment 4 weeks before start of study drug and throughout study duration.\n5. Able to understand the written participant information and give informed consent\n\nExclusion Criteria:\n\n1. Non-diabetic kidney disease indicated by medical history and/or laboratory findings.\n2. eGFR\\< 25 ml/min/1.73m2, dialysis or kidney transplantation.\n3. Previous diabetic ketoacidosis, except at debut.\n4. Dysregulated diabetes (HbA1c \\> 85 mmol/mol)\n5. Decreased awareness or unawareness\n6. Pregnancy, lactating or with a wish of pregnancy within the next year\n7. Low carbohydrate diet\n8. Receiving therapy with an SGLT inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT inhibitor.\n9. New York Heart Association (NYHA) class IV Congestive Heart Failure at the time of enrolment\n10. Myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment\n11. The receipt of any investigational product 90 days prior to this trial\n12. Unable to participate in study procedures\n13. Any clinically significant disorder, except for conditions associated with type 1 diabetes, which in the Investigators opinion could interfere with the results of the trial\n14. Participation in another intervention study\n15. Exclusion criteria for MRI: known claustrophobia, known chronic lung disease, surgery within past 6 weeks or having foreign bodies of metal in the body (e.g. pacemaker, metal plates, metal screws)\n16. Recurrent urogenital infections.'}, 'identificationModule': {'nctId': 'NCT06147232', 'acronym': 'PLUTO', 'briefTitle': 'Prevention of Chronic Kidney Disease(CDK) Progression in Type 1 Diabetes With Long Term Use of Sodium-Glucose-coTransporter Inhibitors Avoiding Kidney hypOxia', 'organization': {'class': 'OTHER', 'fullName': 'Steno Diabetes Center Copenhagen'}, 'officialTitle': 'Prevention of CKD Progression in Type 1 Diabetes With Long Term Use of SGLTi Avoiding Kidney hypOxia(PLUTO)', 'orgStudyIdInfo': {'id': 'EUCT 2023-509450-55-00'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'order: placebo/sotagliflozin', 'description': 'first treatment period: 12 weeks placebo follow by: 6 weeks washout second treatment period: 12 weeks Sotagliflozin 200mg', 'interventionNames': ['Drug: Sotagliflozin', 'Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'order: sotagliflozin/placebo', 'description': 'first treatment period: 12 weeks Sotagliflozin 200mg follow by: 6 weeks washout second treatment period: 12 weeks placebo', 'interventionNames': ['Drug: Sotagliflozin', 'Drug: Placebo']}], 'interventions': [{'name': 'Sotagliflozin', 'type': 'DRUG', 'otherNames': ['Inpefa (TM)'], 'description': 'Sodium-glucose-co-transporter 1 and 2 inhibitor', 'armGroupLabels': ['order: placebo/sotagliflozin', 'order: sotagliflozin/placebo']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo tablet', 'armGroupLabels': ['order: placebo/sotagliflozin', 'order: sotagliflozin/placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '2730', 'city': 'Herlev', 'country': 'Denmark', 'contacts': [{'name': 'Mette Brouw Iversen, MD', 'role': 'CONTACT', 'email': 'mette.brouw.iversen@regionh.dk', 'phone': '004529267717'}, {'name': 'Elisabeth Stougaard, MD, PhD', 'role': 'CONTACT', 'email': 'elisabeth.buur.stougaard@regionh.dk', 'phone': '004522436292'}, {'name': 'Peter Rossing, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Mette Brouw Iversen, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Elisabeth Stougaard, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Emilie Frimodt-Moeller, MD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Steno Diabetes Center Copenhagen', 'geoPoint': {'lat': 55.72366, 'lon': 12.43998}}, {'city': 'London', 'country': 'United Kingdom', 'contacts': [{'name': 'Karalliedde, MD, PhD, MPH', 'role': 'CONTACT', 'email': 'j.karalliedde@kcl.ac.uk', 'phone': '44+020 7188 1981'}], 'facility': "Guy's and St Thomas NHS Trust", 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'centralContacts': [{'name': 'Mette Brouw Iversen, MD', 'role': 'CONTACT', 'email': 'mette.brouw.iversen@regionh.dk', 'phone': '+4529267717'}, {'name': 'Peter Rossing, MD, DMSc', 'role': 'CONTACT', 'email': 'peter.rossing@regionh.dk', 'phone': '+4530913383'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Steno Diabetes Center Copenhagen', 'class': 'OTHER'}, 'collaborators': [{'name': 'Juvenile Diabetes Research Foundation', 'class': 'OTHER'}, {'name': "King's College London", 'class': 'OTHER'}, {'name': 'Glostrup University Hospital, Copenhagen', 'class': 'OTHER'}, {'name': "Guy's and St Thomas' NHS Foundation Trust", 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}