NephropathyPhase 2PLUTONCT06147232
Prevention of Chronic Kidney Disease(CDK) Progression in Type 1 Diabetes With Long Term Use of Sodium-Glucose-coTransporter Inhibitors Avoiding Kidney hypOxia
A Phase 2 study testing Sotagliflozin in people with Nephropathy and Diabetic Nephropathies, run by Steno Diabetes Center Copenhagen at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nephropathy, Diabetic Nephropathies, Diabetes Mellitus, Type 1
- What is being tested?
- Sotagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Feb 2025to May 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Denmark1 site
Steno Diabetes Center Copenhagen
Herlev, 2730
Mette Brouw Iversen, MD, 004529267717, mette.brouw.iversen@regionh.dk
Elisabeth Stougaard, MD, PhD, 004522436292, elisabeth.buur.stougaard@regionh.dk
United Kingdom1 site
Guy's and St Thomas NHS Trust
London
Karalliedde, MD, PhD, MPH, 44+020 7188 1981, j.karalliedde@kcl.ac.uk
About this study
Official title: Prevention of CKD Progression in Type 1 Diabetes With Long Term Use of SGLTi Avoiding Kidney hypOxia(PLUTO)
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.
Read more
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
- Being tested
- Sotagliflozin, Placebo
- Medical subject headings
- Kidney Diseases, Diabetic Nephropathies, Diabetes Mellitus, Type 1, Albuminuria, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SotagliflozinDrug
Also called Inpefa (TM)
Sodium-glucose-co-transporter 1 and 2 inhibitor
PlaceboDrug
Placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| order: placebo/sotagliflozin | Experimental | first treatment period: 12 weeks placebo follow by: 6 weeks washout second treatment period: 12 weeks Sotagliflozin 200mg Receives: 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 Receives: Drug: Sotagliflozin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 0 to 12 weeks in both treatment arms, last measure 30 weeks after randomization.
Secondary outcomes (12)
Change in renal perfusion (medullary and cortical)
Measured with MRI by arterial spin labelling in mL/g/min
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization
Change in renal artery flow
Renal artery flow measured by using phase contrast (PC) MRI. It is measured in mL/min.
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization
Change in renal oxygen consumption
Renal oxygen consumption measured by MRI with T2-relaxation-under-spin-tagging.
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization
Change in renal parenchymal triglyceride fraction
Renal parenchymal triglyceride fraction is measured by MRI spectroscopy
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization
Change in renal fibrosis
Renal fibrosis is measured by MRI-derived apparent diffusion coefficient
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization
Change in left ventricular ejection fraction
Left ventricular ejection fraction is assessed by MRI
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization
Change in albuminuria
Urinary albumin-creatinine ratio (UACR) - morning void spot urine samples collected at home by participants.
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.
Change in levels of ketone bodies
Capillary blood ketones, possibly measured by continous ketone monitoring device
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.
Change in plasma and urine inflammation- and fibrosis biomarkers
Measured from blood and urine samples using a commercially available panel from the company Olink. Includes 92 biomarkers.
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.
Change in endogenous erythropoietin
Analysis on blood samples at regional hospital laboratory.
Measured: From 0 to 12 weeks in each treatment arm. Last measure 30 weeks after randomization.
Change in pro brain natriuretic peptide
Analysis on blood samples at regional hospital laboratory.
Measured: 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
Glomerular filtration rate. At Steno Diabetes Center Copenhagen this will be measured by plasma clearance of Tc-99m diethylene-triamine-pentaacetate.
Measured: From 12 to 30 weeks after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2023
- Study startFeb 2025 (estimated)
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NephropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- randomized, double-blinded, placebo-controlled, cross-over intervention study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 69 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, King's College London, Glostrup University Hospital, Copenhagen, Guy's and St Thomas' NHS Foundation Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06147232
- Sponsor's protocol ID
- EUCT 2023-509450-55-00
- Acronym
- PLUTO
- Status last verified
- Jan 2025
- First submitted
- 19 Nov 2023
- Last updated
- 27 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of CKD Progression in Type 1 Diabetes With Long Term Use of SGLTi Avoiding Kidney hypOxia(PLUTO)
- ClinicalTrials.gov ID
- NCT06147232
- Acronym / sponsor ID
- PLUTO / EUCT 2023-509450-55-00
- Conditions
- Nephropathy, Diabetic Nephropathies, Diabetes Mellitus, Type 1, Albuminuria, Diabetic Complications Renal, Diabetic Complications Cardiovascular
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 69 participants (estimated)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, King's College London, Glostrup University Hospital, Copenhagen, Guy's and St Thomas' NHS Foundation Trust
- Study start
- Feb 2025 (estimated)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 27 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- randomized, double-blinded, placebo-controlled, cross-over intervention study
| Arm | Type | Receives |
|---|---|---|
| order: placebo/sotagliflozin | Experimental | Drug: Sotagliflozin, Drug: Placebofirst treatment period: 12 weeks placebo follow by: 6 weeks washout second treatment period: 12 weeks Sotagliflozin 200mg |
| order: sotagliflozin/placebo | Experimental | Drug: Sotagliflozin, Drug: Placebofirst treatment period: 12 weeks Sotagliflozin 200mg follow by: 6 weeks washout second treatment period: 12 weeks placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SotagliflozinAlso: Inpefa (TM)Sodium-glucose-co-transporter 1 and 2 inhibitor | Drug | order: placebo/sotagliflozin, order: sotagliflozin/placebo |
| PlaceboPlacebo tablet | Drug | order: placebo/sotagliflozin, order: sotagliflozin/placebo |
Primary outcome
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.
difference between change from 0 to 12 weeks after treatment with sotagliflozin compared to treatment with placebo
12 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sotagliflozin in people with Nephropathy and Diabetic Nephropathies, run by Steno Diabetes Center Copenhagen at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mette Brouw Iversen, MD (+4529267717, mette.brouw.iversen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.