Dapagliflozin and Hydrochlorothiazide in Recurring Kidney Stone Patients

Dapagliflozin and Hydrochlorothiazide Treatment in Recurring Kidney Stone Patients - a Randomised Single Center Cross-over Study

Current prevention strategies in patients with recurrence of kidney stones show especially in high-risk patients a diversely and in the long-term not successful outcome in a sustainable number of cases. Recent studies have revealed that Dapagliflozin has the potential to decrease risk and incidence of urolithiasis events especially in patients suffering from Diabetes. The investigators propose that Dapagliflozin has the potential to increase the metabolic situation of hyperoxaluric patients with recurrence of urolithiasis. The investigators therefore test whether Dapagliflozin can decrease the oxalate excretion compared to the current strategy with Hydrochlorothiazide. The study may open up a new way of preventing urolithiasis in patients with high-risk of recurring urolithiasis.

Study Overview

• Status: Not yet recruiting
• Conditions: Urolithiasis; Hyperoxaluria
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zeljko Kikic, Assoc.Prof.Priv.Doz.Dr; Phone Number: 0043 (0)1 40400 43910; Email: zeljko.kikic@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Calcium-oxalate stone formers with high risk of reoccurrence defined as:

• At least two symptomatic or surgically treated kidney stones within the last 10 years and/or
• Single stone kidney formers with risk factors including: a.) Positive medical family history on kidney stone formations of at least one blood related relative in the first degree or at least two blood related relatives in the second degree and/ or b.) Onset of kidney stone formations within the third life decade or earlier and/ or c.) Metabolic syndrome d.) Obesity (BMI ≥ 30 kg/m²)

Exclusion Criteria:

• Age < 18 years
• Malabsorption disorder
• eGFR < 30 ml/min/1,73 m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Washout Phase and treatment arms; At first there will be wash-out phase I with daily placebo administration for all participants. All patients will receive blood- and 24h-urine screenings in week 0 and 6 to get baseline data and also a low-dose native CT of the urinary tract in week 6. In preparation of the HCT phase all participants will daily receive an oral placebo. In week 7 the HCT phase will start and all patients will receive an oral therapy with 50mg of HCT daily; the treatment response will be evaluated by blood- and urine test after 4 weeks of therapy (week 10). After that, in washout phase II, the same test as before will be performed in week 0 and 6 (weeks 15 and 20). At the end another therapy phase with an oral administration of 10mg dapagliflozin daily will be performed; the treatment response will be evaluated by blood- and urine test after 4 weeks of therapy (week 25). Finally, the same tests as before will be performed in wash-out phase III in week 0 and 6 (weeks 29 and 34).

Drug: Dapagliflozin; 10mg Dapagliflozin daily for 8 weeks; Drug: Hydrochlorothiazide; 50mg Hydrochlorothiazide daily for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Δ of urinary oxalate excretion	As the primary endpoint the investigators defined the change of the urine oxalate excretion assessed by 24 h hour urine by 25% after 8 weeks of SGLT-2 inhibitor therapy compared to the baseline value that was collected in the washout phase before the treatment period. (Δ week0 and week 8 in mmol/L)	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of serum kreatinine	Change of serum kreatinine (in mg/dL) assessed by blood collection after 8 weeks of SGLT-2 inhibitor therapy compared to the baseline value that was collected in the washout phase before the treatment period.	8 weeks
Frequency of urolithiasis	Frequency of sympothomatic or treatment worthy urolithiasis events within the 12 month lasting afterward study period. (in events/ person/ year)	12 months
Tolerability of SGLT-2inhibitor therapy	Tolerability of the SGLT-2 inhibitors within 8 weeks lasting therapy phase assessed by a physician in [Type of adverse event; Start (date and time); End (date and time); Severity (mild, moderate, severe); Serious (no / yes); Unexpected (no / yes); Outcome (resolved, resolving, not resolved, resolved with sequelae, unknown, fatal); Relation to study drug (Related/ Probably/ Possibly/ Unlikely/ Not related/ Not assessable)].	8 weeks
Change of eGFR	Change of eGFR (in ml/min/1,73 m2) that was calculated from serum kreatinine that was assessed by blood collection after 8 weeks of SGLT-2 inhibitor therapy compared to the baseline value that was collected in the washout phase before the treatment period.	8 weeks
Δ of urinary calcium excretion	Reduction of the urine calcium excretion assessed by 24 h hour urine by 25% after 8 weeks of SGLT-2 inhibitor therapy compared to the baseline value that was collected in the washout phase before the treatment period. (Δ week0 and week 8 in mmol/L)	8 weeks

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Estimated): March 4, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Urolithiasis; Hyperoxaluria
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Calculi; Nephrolithiasis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Calculi; Urolithiasis; Kidney Calculi; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium-Glucose Transporter 2 Inhibitors; Sodium Chloride Symporter Inhibitors; Dapagliflozin; Hydrochlorothiazide
• Other Study ID Numbers: Urolithiasis

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