Dapagliflozin and Hydrochlorothiazide in Recurring Kidney Stone Patients

NCT05443932 | Unknown Phase 4

• 1 other identifier: Urolithiasis
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Urolithiasis; Hyperoxaluria

Keywords

Urolithiasis; Hyperoxaluria

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Δ of urinary calcium excretion

  8 weeks

• Change of serum kreatinine

  8 weeks

• Frequency of urolithiasis

  12 months

• Tolerability of SGLT-2inhibitor therapy

  8 weeks

• Change of eGFR

  8 weeks

Study Arms (1)

Washout Phase and treatment arms

OTHER

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; Drug: Hydrochlorothiazide

Interventions

Dapagliflozin DRUG

10mg Dapagliflozin daily for 8 weeks

Washout Phase and treatment arms

Hydrochlorothiazide DRUG

50mg Hydrochlorothiazide daily for 8 weeks

Washout Phase and treatment arms

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Urolithiasis; Hyperoxaluria

Interventions

dapagliflozin; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Zeljko Kikic, Assoc.Prof.Priv.Doz.Dr

CONTACT

0043 (0)1 40400 43910; zeljko.kikic@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof.Priv.Doz.Dr.

Model Details: There won´t be comparator arms in our study. Instead, the investigators plan to do blood- and 24h-urine screenings including oxalate and citrate as well as metabolomics tests out of blood and urine samples at crucial points of time of the study to get baseline and therapeutic data of the participants.

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: July 5, 2022
• Study Start: March 4, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: October 23, 2023

Record last verified: 2023-10

Locations

AU (1)