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

NCT06147232 | Not Yet Recruiting Phase 2

• 1 other identifier: EUCT 2023-509450-55-00
• Study Type: interventional
• Target: 69
• Locations: 2 countries
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in dynamic R2*-weighted signal (BOLD) as an indirect measure of renal blood oxygenation

  difference between change from 0 to 12 weeks after treatment with sotagliflozin compared to treatment with placebo

  0 to 12 weeks in both treatment arms, last measure 30 weeks after randomization.

Secondary Outcomes (12)

• Change in renal perfusion (medullary and cortical)

  From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization

• Change in renal artery flow

  From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization

• Change in renal oxygen consumption

  From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization

• Change in renal parenchymal triglyceride fraction

  From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization

• Change in renal fibrosis

  From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization

Other Outcomes (1)

• Ethnicity

  From baseline to 30 weeks.

Study Arms (2)

order: placebo/sotagliflozin

EXPERIMENTAL

first treatment period: 12 weeks placebo follow by: 6 weeks washout second treatment period: 12 weeks Sotagliflozin 200mg

Drug: Sotagliflozin; Drug: Placebo

order: sotagliflozin/placebo

EXPERIMENTAL

first treatment period: 12 weeks Sotagliflozin 200mg follow by: 6 weeks washout second treatment period: 12 weeks placebo

Drug: Sotagliflozin; Drug: Placebo

Interventions

Sotagliflozin DRUG

Sodium-glucose-co-transporter 1 and 2 inhibitor

Also known as: Inpefa (TM)

order: placebo/sotagliflozin; order: sotagliflozin/placebo

Placebo DRUG

Placebo tablet

order: placebo/sotagliflozin; order: sotagliflozin/placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Recurrent urogenital infections.

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• Juvenile Diabetes Research Foundation: collaborator
• King's College London: collaborator
• Glostrup University Hospital, Copenhagen: collaborator
• Guy's and St Thomas' NHS Foundation Trust: collaborator

Study Sites (2)

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

Location

Guy's and St Thomas NHS Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus, Type 1; Albuminuria; Hypoxia

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory

Central Study Contacts

Mette Brouw Iversen, MD

CONTACT

+4529267717; mette.brouw.iversen@regionh.dk

Peter Rossing, MD, DMSc

CONTACT

+4530913383; peter.rossing@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, double-blinded, placebo-controlled, cross-over intervention study

Study Record Dates

• First Submitted: November 19, 2023
• First Posted: November 27, 2023
• Study Start: February 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); DK (1)