A Phase 3 interventional study of Empagliflozin 10 MG and Placebo in Kidney Stone, Nephrolithiasis and Dietary Exposure, sponsored by Insel Gruppe AG, University Hospital Bern. Recruiting at 21 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-23.
Sponsored by Insel Gruppe AG, University Hospital Bern · Phase 3, Interventional, and Prevention
The aim of this randomized trial with a 2-by-2 factorial design is to test the efficacy of the SGLT2 inhibitor empagliflozin and personalized dietary counseling based on 24-hr urine collection results and dietary assessments for kidney stone recurrence prevention in patients with calcium kidney stones.
Study interventions:
Control interventions:
Background and rationale:
Nephrolithiasis is a highly prevalent kidney disorder causing substantial morbidity, reduced quality of life and enormous healthcare expenditures worldwide, in large part related to their frequent recurrence. Existing pharmacological strategies for recurrence prevention are limited, and non-pharmacological measures, predominantly dietary counseling practices, vary widely. In observational studies and post-hoc analyses of cardiovascular outcome trials, Sodium-Glucose Co-Transporter 2 inhibitor (SGLT2i) use was associated with a 26-49 % reduction in kidney stone events in patients with type 2 diabetes. In our recent randomized phase 2 SWEETSTONE trial (NCT04911660), the SGLT2i empagliflozin reduced the urinary relative supersaturation ratio for calcium phosphate by 36 % compared to placebo in non-diabetic patients with idiopathic calcium kidney stones, by far the most common kidney stone type. The therapeutic value of SGLT2is in prevention of kidney stone recurrence is unknown, and the optimal dietary counseling approach for patients with kidney stones is undefined.
Objectives:
The primary objective of the study is to assess the efficacy of empagliflozin and a personalized dietary counseling strategy in the secondary prevention of calcium kidney stones, assessed as radiologic stone recurrence at 3 years.
The secondary objectives of the study are to assess the effect of the interventions (empagliflozin versus placebo and personalized versus generic dietary counseling) on both the recurrence and cumulative number of symptomatic kidney stones within 3 years.
Methodology:
The investigators will include 400adult (≥ 18 years) patients with recurrent (≥ 2 kidney stone episodes in the last 10 years) calcium kidney stones (containing 50% or more of calcium oxalate, calcium phosphate or a mixture of both). Patients with known secondary causes of kidney stones will be excluded. In this randomized trial with a 2-by-2 factorial design, patients will be allocated to either empagliflozin 10mg or placebo once daily, and to either personalized or generic dietary counselling according to 24-hr urine results. Randomization will be stratified according to the number of kidney stone episodes during the 10 years before enrolment.
The primary endpoint will be radiologic kidney stone recurrence (a composite of stone growth or new stones formed assessed by computed tomography) at 3 years. Secondary endpoints will be symptomatic kidney stone recurrence up to 3 years, and the number of symptomatic recurrences over 3 years. Exploratory endpoints will be changes in blood and urine parameters, vital signs and weight; asymptomatic kidney stone passage; patient-reported pain and quality of life; and kidney stone event-related health care utilization and cost. Safety endpoints assessed will be the frequency of serious adverse events and of pre-defined adverse events of special interest.
509 studies on the registry are indexed under Kidney Calculi; 146 are open to participants now.
This study's planned enrollment of 400 is above the median of 86 across 391 interventional studies indexed under Kidney Calculi.
Browse Kidney Calculi studies →Insel Gruppe AG, University Hospital Bern is the lead sponsor of 741 studies on the registry; 180 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Empagliflozin 10 mg once daily per os and personalized dietary counseling for 3 years
Drug: Empagliflozin 10 MG · Behavioral: Personalized dietary counseling
Placebo once daily per os and personalized dietary counseling for 3 years
Drug: Placebo · Behavioral: Personalized dietary counseling
Empagliflozin 10 mg once daily per os and generic dietary counseling for 3 years
Drug: Empagliflozin 10 MG · Behavioral: Generic dietary counseling
Placebo once daily per os and generic dietary counseling for 3 years
Drug: Placebo · Behavioral: Generic dietary counseling
Once daily per os for 3 years
Once daily per os for 3 years
Personalized dietary counseling based on repeat 24-hr urine collections and dietary assessments for 3 years
Generic dietary counseling based on current guidelines without 24-hr urine collection results and without specific dietary assessments for 3 years
Number of patients with radiologic stone recurrence
Radiological stone recurrence is defined as a new stone formed or enlargement of a preexisting stone (assessed by low-dose CT of the kidney at the end of the study compared to the low-dose CT of the kidney at the baseline visit).
Time frame: After 3 years
Time to symptomatic kidney stone recurrence up to 3 years (time-to-event)
Symptomatic recurrence is defined as the visible passage of a stone with or without accompanying typical symptoms (such as flank or loin pain and hematuria) or as the presence of a symptomatic or asymptomatic stone that was determined to require surgical removal.
Time frame: From enrollment to the end of treatment at 3 years
Number of symptomatic stone recurrences per patient (cumulative)
Symptomatic recurrence is defined as the visible passage of a stone with or without accompanying typical symptoms (such as flank or loin pain and hematuria) or as the presence of a symptomatic or asymptomatic stone that was determined to require surgical removal.
Time frame: From enrollment to the end of treatment at 3 years
Changes in blood parameters
Blood parameters will be measured at screening, Month 3, Year 1, Year 2 and Year 3.
Time frame: From enrollment to the end of treatment at 3 years
Changes in urine parameters
24-hr urine analyses will be done at screening, Month 3, Year 1, Year 2 and Year 3. Note: results of 24-hr urine analyses will be blinded until the end of the study in patients randomized to generic dietary counselling.
Time frame: From enrollment to the end of treatment at 3 years
Changes in blood pressure
Blood pressure measurements will be done at screening, Month 3, Year 1, Year 2 and Year 3.
Time frame: From enrollment to the end of treatment at 3 years
Changes in weight
Weight, will be measured at screening, Month 3, Year 1, Year 2 and Year 3.
Time frame: From enrollment to the end of treatment at 3 years
Changes in hip and waist circumference
Hip and waist circumference will be measured at screening, Month 3, Year 1, Year 2 and Year 3
Time frame: From enrollment to the end of treatment at 3 years
Patient-reported kidney stone-related quality of life
Patient-reported kidney stone-related quality of life will be assessed by the Wisconsin Stone-Quality of Life (WSQoL) questionnaire at baseline, Month 3, Year 1, Year 2 and Year 3. Higher scores indicate better quality of life.
Time frame: From enrollment to the end of treatment at 3 years
Patient-reported health-related quality of life (HRQoL)
Patient-reported HRQoL will be assessed by using the short form-36 version 2 (SF-36v2) questionnaire at baseline, Month 3, Year 1, Year 2 and Year 3. Higher scores indicate higher HRQoL.
Time frame: From enrollment to the end of treatment at 3 years
Number of patients with asymptomatic kidney stone passage
Asymptomatic passage is defined as a stone present on the baseline CT but not on the end of study CT without causing any symptoms in the patient.
Time frame: At 3 years
Kidney stone-related health care utilization
Data on health care visits, hospitalizations, and surgical interventions in relation to kidney stone disease
Time frame: From enrollment to the end of treatment at 3 years
Kidney stone-related cost
Total kidney stone-related cost (direct and indirect).
Time frame: From enrollment to the end of treatment at 3 years
Changes in bone mineral density
Changes in NCCT-based bone mineral density measured at lumbar vertebrae
Time frame: From enrollment to end of treatment at 3 years
Changes in aortic artery calcification
Changes in NCCT-based aortic artery calcification by the Agaston method
Time frame: From enrollment to end of treatment at 3 years
Changes in adipose tissue
Changes in NCCT-based visceral, subcutaneous and total adipose tissue (VAT/TAT and VAT/TAT ratios)
Time frame: From enrollment to end of treatment at 3 years
Plan to share: No — Once results have been published, trial data will be accessible to external researchers and coded datasets corresponding to each publication will be made available. Investigators wishing to replicate the analyses or to do an individual patient meta-analysis may request the data to the Sponsor-Investigator.
Started Jul 2026 (actual). Primary completion is estimated for Sep 2030, 50 months after the start.
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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