PLUTO - Prevention of CKD progression in type 1 diabetes with Long term Use of SGLTi avoiding kidney hypOxia

Phase 2

Recruiting

Conditions: Type 1 Diabetes Mellitus with chronic kidney complications

Registration Number: 2023-509450-55-01

Lead Sponsor: Steno Diabetes Center Copenhagen

Brief Summary: The primary aim is to estimate the effect of three months treatment with sotagliflozin on renal oxygenation (MRI) in people with T1D and chronic kidney disease

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 39

Inclusion Criteria

Adults with type 1 diabetes mellitus

Chronic Kidney Disease and albuminuria

Exclusion Criteria

Non-diabetic Kidney Disease

eGFR<25mL/min/1.73m^2, dialysis or kidney transplantation

Previous diabetic ketoacidosis, except at debut

Receiving therapy with an SGLT inhibitor within 8 weeks prior to enrolment or previous intolerence of an SGLT inhibitor.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Change from 0 to 12 weeks in dynamic R2*-weighted signal (BOLD) as an indirect measure of renal blood oxygenation after treatment with sotagliflozin compared with placebo.		Change from 0 to 12 weeks in dynamic R2*-weighted signal (BOLD) as an indirect measure of renal blood oxygenation after treatment with sotagliflozin compared with placebo.

Secondary Outcome Measures

Name	Time	Method
Change in renal fibrosis	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization	Renal fibrosis is measured by MRI-derived apparent diffusion coefficient
Change in renal artery flow	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization	Renal artery flow measured by using phase contrast (PC) MRI. It is measured in mL/min.
Change in renal parenchymal triglyceride fraction	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization	Renal parenchymal triglyceride fraction is measured by MRI spectroscopy
Change in renal perfusion (medullary and cortical)	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization	Measured with MRI by arterial spin labelling in mL/g/min
Change in renal oxygen consumption	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization	Renal oxygen consumption measured by MRI with T2-relaxation-under-spin-tagging.
Change in left ventricular ejection fraction	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization	Left ventricular ejection fraction is assessed by MRI
Change in albuminuria	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.	Urinary albumin-creatinine ratio (UACR) - morning void spot urine samples collected at home by participants.
Change in levels of ketone bodies	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.	Capillary blood ketones, possibly measured by continous ketone monitoring device
Change in plasma and urine inflammation- and fibrosis biomarkers	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.	Measured from blood and urine samples using a commercially available panel from the company Olink. Includes 92 biomarkers.
Change in endogenous erythropoietin	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.	Analysis on blood samples at regional hospital laboratory.
Difference in Kidney Function after 12 weeks treatment with sotagliflozin vs placebo	From 12 to 30 weeks after randomization	Glomerular filtration rate. At Steno Diabetes Center Copenhagen this will be measured by plasma clearance of Tc-99m diethylene-triamine-pentaacetate.
Change in pro brain natriuretic peptide	From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.	Analysis on blood samples at regional hospital laboratory.

Trial Locations

Locations (1): Steno Diabetes Center Copenhagen
🇩🇰
Herlev, Denmark
Steno Diabetes Center Copenhagen
🇩🇰Herlev, Denmark
Peter Rossing
Site contact
+4530913383
peter.rossing@regionh.dk