Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers

NCT04911660 | Completed Phase 2

• 1 other identifier: 2020-02679
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to test the effect of a new drug on the composition of the urine in kidney stone patients. This new drug (Jardiance®, substance: empagliflozin) is currently approved in Switzerland for the treatment of patients with diabetes. Data from previous studies with and without diabetes suggest that it may have a beneficial effect on the composition of the urine and thereby reduce the risk of developing kidney stones.

Conditions

Kidney Stone

Keywords

Kidney stones; Empagliflozin; Supersaturation

Outcome Measures

Primary Outcomes (6)

• Primary outcome component 1 - calcium oxalate supersaturation in urine (empagliflozin treatment)

  The primary endpoint is composed of three primary outcomes that will be assessed separately. 1\) change in calcium oxalate supersaturation after empagliflozin treatment Calcium oxalate supersaturation will be calculated by the Equil-2 program from the oxalate concentration in urine.

  Oxalate supersaturation will be determined at baseline and after 14 days treatment with empagliflozin

• Primary outcome component 1 - calcium oxalate supersaturation in urine (placebo treatment)

  The primary endpoint is composed of three primary outcomes that will be assessed separately. 1\) change in calcium oxalate supersaturation after placebo treatment as a comparator for empagliflozin treatment Calcium oxalate supersaturation will be calculated by the Equil-2 program from the oxalate concentration in urine.

  Oxalate supersaturation will be determined at baseline and after 14 days treatment with placebo

• Primary outcome component 2 - calcium phosphate supersaturation in urine (empagliflozin treatment)

  The primary endpoint is composed of three primary outcomes that will be assessed separately. 2\) change in calcium phosphate supersaturation after empagliflozin treatment Calcium phosphate supersaturation will be calculated by the Equil-2 program from the calcium phosphate concentration in urine.

  Calcium phosphate supersaturation will be determined at baseline and after 14 days treatment with empagliflozin

• Primary outcome component 2 - calcium phosphate supersaturation in urine (placebo treatment)

  The primary endpoint is composed of three primary outcomes that will be assessed separately. 2\) change in calcium phosphate supersaturation after placebo treatment as a comparator for empagliflozin treatment Calcium phosphate supersaturation will be calculated by the Equil-2 program from the calcium phosphate concentration in urine.

  Calcium phosphate supersaturation will be determined at baseline and after 14 days treatment with placebo

• Primary outcome component 3 - uric acid supersaturation in urine (empagliflozin treatment)

  The primary endpoint is composed of three primary outcomes that will be assessed separately. 3\) change in uric acid supersaturation after empagliflozin treatment Uric acid supersaturation will be calculated by the Equil-2 program from the uric acid concentration in urine.

  Uric acid supersaturation will be determined at baseline and after 14 days treatment with empagliflozin

• Primary outcome component 3 - uric acid supersaturation in urine (placebo treatment)

  The primary endpoint is composed of three primary outcomes that will be assessed separately. 3\) change in uric acid supersaturation after placebo treatment as a comparator for empagliflozin treatment Uric acid supersaturation will be calculated by the Equil-2 program from the uric acid concentration in urine.

  Uric acid supersaturation will be determined at baseline and after 14 days treatment with placebo

Secondary Outcomes (47)

• Blood sodium level change from baseline

  Data collected at baseline, after 1st 14 days treatment and after 2nd 14 days treatment expected to be 6-10 weeks from baseline.

• Blood potassium level change from baseline

  Data collected at baseline, after 1st 14 days treatment and after 2nd 14 days treatment expected to be 6-10 weeks from baseline.

• Blood chloride level change from baseline

  Data collected at baseline, after 1st 14 days treatment and after 2nd 14 days treatment expected to be 6-10 weeks from baseline.

• Blood total calcium level change from baseline

  Data collected at baseline, after 1st 14 days treatment and after 2nd 14 days treatment expected to be 6-10 weeks from baseline.

• Blood ionized calcium level change from baseline

  Data collected at baseline, after 1st 14 days treatment and after 2nd 14 days treatment expected to be 6-10 weeks from baseline.

Study Arms (2)

Empagliflozin + Placebo

ACTIVE COMPARATOR

1 capsule containing 25 mg empagliflozin per day for 14 days, followed by a 14-42 days wash-out phase and a second treatment phase with 1 capsule containing placebo for 14 days.

Drug: Empagliflozin 25 MG; Other: Placebo

Placebo + Empagliflozin

PLACEBO COMPARATOR

1 capsule containing placebo per day for 14 days, followed by a 14-42 days wash-out phase and a second treatment phase with 1 capsule containing 25 mg empagliflozin for 14 days.

Drug: Empagliflozin 25 MG; Other: Placebo

Interventions

Empagliflozin 25 MG DRUG

1 empagliflozin 25 mg capsule per day for 14 days

Empagliflozin + Placebo; Placebo + Empagliflozin

Placebo OTHER

1 placebo capsule per day for 14 days

Empagliflozin + Placebo; Placebo + Empagliflozin

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent as documented by signature
• Age between 18 and 74 years old
• One or more kidney stone event(s) in the past
• Any past kidney stone containing ≥ 80 % of calcium or ≥ 80 % of uric acid
• HbA1c \< 6.5 %

You may not qualify if:

• Patients with secondary causes of recurrent nephrolithiasis:
• Severe eating disorders (anorexia or bulimia)
• Chronic bowel disease, past intestinal or bariatric surgery
• Sarcoidosis
• Primary hyperparathyroidism
• Complete distal tubular acidosis
• Patients with the following medications:
• Anti-diabetic treatment (insulin and non-insulin agents)
• Patients not able or not willing to stop the following medication during the period of participation in the trial (including a time window of 4 weeks wash out prior to randomization):
• Diuretics (thiazide and loop diuretics)
• Carbonic anhydrase inhibitors (including topiramate)
• Xanthine oxidase inhibitors
• Alkali, including potassium citrate or sodium bicarbonate
• Treatment with 1,25-OH Vitamin D (calcitriol)
• Calcium supplementation

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Boehringer Ingelheim: collaborator
• University of Bern: collaborator

Study Sites (1)

Inselspital, Department of Nephrology and Hypertension

Bern, 3010, Switzerland

Location

Related Publications (2)

• Anderegg MA, Schietzel S, Bargagli M, Bally L, Faller N, Moor MB, Cereghetti GM, Roumet M, Trelle S, Fuster DG. Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial. Nat Med. 2025 Jan;31(1):286-293. doi: 10.1038/s41591-024-03330-x. Epub 2025 Jan 2.

  PMID: 39747681 DERIVED

• Schietzel S, Bally L, Cereghetti G, Faller N, Moor MB, Vogt B, Rintelen F, Trelle S, Fuster D. Impact of the SGLT2 inhibitor empagliflozin on urinary supersaturations in kidney stone formers (SWEETSTONE trial): protocol for a randomised, double-blind, placebo-controlled cross-over trial. BMJ Open. 2022 Mar 14;12(3):e059073. doi: 10.1136/bmjopen-2021-059073.

  PMID: 35288397 DERIVED

MeSH Terms

Conditions

Kidney Calculi

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Nephrolithiasis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Urinary Calculi; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel Fuster, MD

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Empagliflozin and placebo will be provided in identically looking bottles. Besides the consecutive number, packs and pack content will look identical. Therefore, all trial personnel that is involved in recruitment and care of patients, trial assessment, monitoring and analyses will be blinded to the assigned trial arm.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible individuals will be randomized in equal proportions to 25 mg empagliflozin or placebo, taken once daily per os in the morning. Placebo will be administered to individuals randomized to that treatment in a form identical to empagliflozin. Patients will remain on the assigned IMP for 14 days. The following 14 days (days 15 - 28) will be a wash out period without IMP intake; this wash out time can be extended to up to 6 weeks if necessary. On day 29 of the study (or later according to the length of the wash out phase), a second 14 days period with IMP intake starts (empagliflozin or placebo, whichever was not received initially).

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: June 3, 2021
• Study Start: August 25, 2021
• Primary Completion: March 30, 2023
• Study Completion: April 28, 2023
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)