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ClinicalTrials.gov ID

NCT06147232

Lead Sponsor

Steno Diabetes Center CopenhagenOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 2

Enrollment

69Estimated

Last Update Posted

Jan 27, 2025Actual

Start Date

Feb 2025Estimated

Primary Completion Date

May 2027Estimated

Completion Date

May 2027Estimated

Official Title

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

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.

• Nephropathy
• Diabetic Nephropathies
• Diabetes Mellitus, Type 1
• Albuminuria
• Diabetic Complications Renal
• Diabetic Complications Cardiovascular
• Hypoxia

• Sotagliflozin
• Placebo

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility 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.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Crossover Assignment

Masking

Triple

Lead Sponsor

Steno Diabetes Center CopenhagenOTHER

Collaborators

Juvenile Diabetes Research FoundationOTHER

King's College LondonOTHER

Glostrup University Hospital, CopenhagenOTHER

Guy's and St Thomas' NHS Foundation TrustOTHER

j.karalliedde@kcl.ac.uk44+020 7188 1981