Autosomal Dominant Polycystic Kidney Disease
Conditions
Keywords
phosphate, calcium, magnesium, Empagliflozin, ADPKD
Brief summary
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.
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.
Interventions
DRUGEmpagliflozin
Empagliflozin 10mg
DRUGPlacebo
Placebo capsule
Sponsors
University of Zurich
Cantonal Hospital Graubuenden
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Investigator-initiated randomised, single-blind, placebo-controlled, cross-over study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome | After a two week intervention | \- Calcium, phosphate, magnesium excretion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome | After a two week intervention | \- 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) |
Countries
Switzerland
Contacts
Primary ContactPatrick Hofmann, MD
Backup ContactThomas Fehr, MD
Outcome results
None listed