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NCT06147232 | NOT YET RECRUITING | Nephropathy

Prevention of Chronic Kidney Disease(CDK) Progression in Type 1 Diabetes With Long Term Use of Sodium-Glucose-coTransporter Inhibitors Avoiding Kidney hypOxia
Sponsor:

Steno Diabetes Center Copenhagen

Brief Summary:

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. Objective: 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. Further aims are to study if renal oxygen consumption and response to SGLT-inhibition differs between people of African-Caribbean or Northern European decent. Additionally effects on left ventricular ejection fraction, kidney function and biomarkers in blood and urine will be explored. Method: 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. Design: Randomized, double-blinded, placebo-controlled, cross over intervention study. Study 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. Endpoints: 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. Timeframe: Inclusion of patients from february 2024. Last visit september 2025. Presentation spring 2026, publication fall 2026.

Condition or disease

Nephropathy

Diabetic Nephropathies

Diabetes Mellitus, Type 1

Albuminuria

Diabetic Complications Renal

Diabetic Complications Cardiovascular

Hypoxia

Intervention/treatment

Sotagliflozin

Placebo

Phase

PHASE2

Study Type : INTERVENTIONAL
Estimated Enrollment : 69 participants
Masking : TRIPLE
Primary Purpose : TREATMENT
Official Title : Prevention of CKD Progression in Type 1 Diabetes With Long Term Use of SGLTi Avoiding Kidney hypOxia(PLUTO)
Actual Study Start Date : 2025-02
Estimated Primary Completion Date : 2027-05
Estimated Study Completion Date : 2027-05

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion Criteria
  • 1. 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)
  • 2. Albuminuria: UACR \> 100 mg/g (in ≥2 out 3 morning spot urine collections prior to randomization)
  • 3. estimated Glomerular Filtration Rate(eGFR) ≥25 and \< 75 ml/min/1.73m2
  • 4. Participants must be on stable renin-angiotensin system blocking treatment 4 weeks before start of study drug and throughout study duration.
  • 5. Able to understand the written participant information and give informed consent
Exclusion Criteria
  • 1. Non-diabetic kidney disease indicated by medical history and/or laboratory findings.
  • 2. eGFR\< 25 ml/min/1.73m2, dialysis or kidney transplantation.
  • 3. Previous diabetic ketoacidosis, except at debut.
  • 4. Dysregulated diabetes (HbA1c \> 85 mmol/mol)
  • 5. Decreased awareness or unawareness
  • 6. Pregnancy, lactating or with a wish of pregnancy within the next year
  • 7. Low carbohydrate diet
  • 8. Receiving therapy with an SGLT inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT inhibitor.
  • 9. New York Heart Association (NYHA) class IV Congestive Heart Failure at the time of enrolment
  • 10. Myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment
  • 11. The receipt of any investigational product 90 days prior to this trial
  • 12. Unable to participate in study procedures
  • 13. 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
  • 14. Participation in another intervention study
  • 15. 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)
  • 16. Recurrent urogenital infections.
Prevention of Chronic Kidney Disease(CDK) Progression in Type 1 Diabetes With Long Term Use of Sodium-Glucose-coTransporter Inhibitors Avoiding Kidney hypOxia

Location Details

NCT06147232

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How to Participate

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Locations

Not yet recruiting

Denmark,

Steno Diabetes Center Copenhagen

Herlev, Denmark, 2730

Not yet recruiting

United Kingdom,

Guy's and St Thomas NHS Trust

London, United Kingdom,