Dapagliflozin and Hydrochlorothiazide in Recurring Kidney Stone Patients

Sponsor

Medical University of Vienna (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05443932

Collaborator

(none)

Enrollment

Location

Arm

26.9

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urolithiasis Hyperoxaluria	Drug: Dapagliflozin Drug: Hydrochlorothiazide	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Oct 3, 2022

Anticipated Primary Completion Date :

Jul 31, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change of urinary oxalate excretion [8 weeks]
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)

Secondary Outcome Measures

Change of urinary calcium excretion [8 weeks]
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)
Change of serum kreatinine [8 weeks]
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.
Frequency of urolithiasis [12 months]
Frequency of sympothomatic or treatment worthy urolithiasis events within the 12 month lasting afterward study period. (in events/ person/ year)
Tolerability of SGLT-2inhibitor therapy [8 weeks]
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)].
Change of eGFR [8 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)