Short-term Effects of an SGLT2 Inhibitor on Divalent Ions in Autosomal Dominant Polycystic Kidney Disease (SIDIA)

This study aims to better understand electrolyte handling in patients with autosomal dominant polycystic kidney disease treated with the SGLT2 inhibitor Empagliflozin.

Patients will be randomized into two groups and take Empagliflozin or a Placebo for 2 weeks with a wash-out period of 2 weeks. The primary outcome is tubular handling of the divalent ions calcium, phosphate and magnesium. Secondary outcomes include diuresis, safety and tolerability.

Study Overview

• Status: Recruiting
• Conditions: Autosomal Dominant Polycystic Kidney Disease
• Intervention / Treatment: Drug: Placebo; Drug: Empagliflozin

Detailed Description

This investigator-initiated randomised, single-blind, placebo-controlled cross-over study aims to better understand tubular electrolyte handling of divalent ions in patients with autosomal dominant polycystic kidney disease treated with the SGLT2 inhibitor Empagliflozin.

After randomization, at week 0, participants collect 24-hour urine sample and a patient visit to assess vitals and blood tests takes place. After this visit, period 1 starts with a 2-week treatment of either Empagliflozin 10mg or Placebo.

At week 2, the second 24-hour-urine sample and 2. patient visit and blood test take place. After this visit, wash-out period for 2 weeks starts where no study drug will be administered At week 4, the period 2, the crossover-period starts for an additional 2 weeks. At week 6; a final and third 24-hour urine sample, clinical visit and blood test takes place.

At week 3 & 7, a phone consultation will assess safety.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Patrick Hofmann, MD; Phone Number: +4181 256 6305; Email: hofmannpatrick@bluewin.ch
• Study Contact Backup: Name: Thomas Fehr, MD; Phone Number: +4181 256 6305; Email: medizin@ksgr.ch

Study Locations

• Switzerland
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8091
      • Recruiting
      • University Hospital Zurich, Division of Nephrology
      • Contact: Thomas Schachtner, MD
  • Kanton Graubünden
    • Chur, Kanton Graubünden, Switzerland, 7000
      • Recruiting
      • Cantonal Hospital Graubuenden
      • Contact: Patrick Hofmann, MD; Email: medizin@ksgr.ch
      • Sub-Investigator: Lorena Roth, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• - Patients 18-75 years old with ADPKD, defined according to international diagnostic and classification criteria14, treated at Cantonal Hospital Graubünden (KSGR) and the University Hospital Zürich (USZ) independent of baseline treatment with the vasopressin receptor antagonist Tolvaptan
• Informed consent as documented by signature

Exclusion Criteria:

• - renal replacement therapy or kidney allograft recipient
• chronic kidney disease CKD KDIGO Stage G4 (eGFR under 30ml/min/1.73m2)
• patients younger 18 years of age
• Diabetes mellitus type 1
• recurrent urinary tract infections (UTI) defined as more than 3 infections requiring antibiotic treatment or over 1 requiring hospitalization/year.
• Patients with uncontrolled hypertension (defined as ambulatory systolic BP over 180mmHg), liver cirrhosis (Child Pugh B and C)
• Patients not able or not willing to stop the following medications during the study period of participation in the trial:
• Thiazide diuretics
• Carbonic anhydrase inhibitors
• Sodium bicarbonate
• 1, 25 (OH) vitamin D (calcitriol)
• Bisphosphonate, denosumab, teriparatide
• Pregnant or lactating women
• Known allergy to study drug
• Inability to understand and follow the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; Placebo	Drug: Placebo; Placebo capsule
Experimental: Intervention; Empagliflozin 10mg	Drug: Empagliflozin; Empagliflozin 10mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome	- Calcium, phosphate, magnesium excretion	After a two week intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome	- diuresis (24-hour urine volume, 24-hour creatinine, ketonuria, osmolarity, urinary pH) - tubular handling of other electrolytes (Na, K, Cl) - inflammation metabolism (CRP, hemoglobin?) - kidney function (creatinine, uric acid, urea, hemoglobin?) - effect on standardized blood pressure (assessed every two weeks) - bone metabolism (FGF23, PTH, 25-(OH)-D3) - tolerability (patient-reported side effects (nycturia, urinary urgency, lightheadedness, syncope) - safety (bacteriuria, urinary tract infection requiring antibiotic treatment, genital mycosis)	After a two week intervention

Collaborators and Investigators

• Sponsor: Cantonal Hospital Graubuenden
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Thomas Fehr, MD, Cantonal Hospital Graubuenden; Principal Investigator: Patrick Hofmann, MD, Cantonal Hospital Graubuenden

Publications and helpful links

General Publications

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Actual): July 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Empagliflozin; ADPKD; magnesium; calcium; phosphate
• Additional Relevant MeSH Terms: Ciliopathies; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Congenital Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Polycystic Kidney Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Polycystic Kidney, Autosomal Dominant; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; empagliflozin
• Other Study ID Numbers: 2024-00070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The local ethics committee approval does not include individual participant data sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No