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Not yet recruiting NCT06147232

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

Phase II Interventional Nephropathy Diabetic Nephropathies Diabetes Mellitus, Type 1 Albuminuria

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Sotagliflozin, Placebo.
Who it may be relevant to
Registry conditions: Nephropathy, Diabetic Nephropathies, Diabetes Mellitus, Type 1, Albuminuria. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Denmark, United Kingdom
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

Prevention of CKD Progression in Type 1 Diabetes With Long Term Use of SGLTi Avoiding Kidney hypOxia(PLUTO)

Overview

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.

Interventions

  • Drug Sotagliflozin
    Sodium-glucose-co-transporter 1 and 2 inhibitor
  • Drug Placebo
    Placebo tablet

Primary outcome measures

  • Change in dynamic R2*-weighted signal (BOLD) as an indirect measure of renal blood oxygenation [Time frame: 0 to 12 weeks in both treatment arms, last measure 30 weeks after randomization.]
Secondary outcome measures (12)
  • Change in renal perfusion (medullary and cortical) [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]
  • Change in renal artery flow [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]
  • Change in renal oxygen consumption [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]
  • Change in renal parenchymal triglyceride fraction [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]
  • Change in renal fibrosis [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]
  • Change in left ventricular ejection fraction [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization]
  • Change in albuminuria [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]
  • Change in levels of ketone bodies [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]
  • Change in plasma and urine inflammation- and fibrosis biomarkers [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]
  • Change in endogenous erythropoietin [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]
  • Change in pro brain natriuretic peptide [Time frame: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.]
  • Difference in Kidney Function after 12 weeks treatment with sotagliflozin vs placebo [Time frame: From 12 to 30 weeks after randomization]

Eligibility criteria

Inclusion criteria

  • 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)
  • Albuminuria: UACR > 100 mg/g (in ≥2 out 3 morning spot urine collections prior to randomization)
  • estimated Glomerular Filtration Rate(eGFR) ≥25 and < 75 ml/min/1.73m2
  • Participants must be on stable renin-angiotensin system blocking treatment 4 weeks before start of study drug and throughout study duration.
  • Able to understand the written participant information and give informed consent

Exclusion criteria

  • Non-diabetic kidney disease indicated by medical history and/or laboratory findings.
  • eGFR< 25 ml/min/1.73m2, dialysis or kidney transplantation.
  • Previous diabetic ketoacidosis, except at debut.
  • Dysregulated diabetes (HbA1c > 85 mmol/mol)
  • Decreased awareness or unawareness
  • Pregnancy, lactating or with a wish of pregnancy within the next year
  • Low carbohydrate diet
  • Receiving therapy with an SGLT inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT inhibitor.
  • New York Heart Association (NYHA) class IV Congestive Heart Failure at the time of enrolment
  • Myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment
  • The receipt of any investigational product 90 days prior to this trial
  • Unable to participate in study procedures
  • 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
  • Participation in another intervention study
  • 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)
  • Recurrent urogenital infections.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Crossover
Masking
Triple blind
Primary purpose
Treatment

Study locations

Denmark · 1 center
  • Steno Diabetes Center Copenhagen — Herlev
United Kingdom · 1 center
  • Guy's and St Thomas NHS Trust — London

Identifiers

NCT: NCT06147232 · EUCT 2023-509450-55-00

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗