Back to resultsDapagliflozin and Hydrochlorothiazide in Recurring Kidney Stone Patients
Primary Purpose
Urolithiasis, Hyperoxaluria
Status
Not yet recruiting
Phase
Phase 4
Locations
Austria
Study Type
Interventional
Intervention
Dapagliflozin
Hydrochlorothiazide
Sponsored by
About this trial
This is an interventional prevention trial for Urolithiasis focused on measuring Urolithiasis, Hyperoxaluria
Eligibility Criteria
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
Sites / Locations
- Medical University of Vienna
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Washout Phase and treatment arms
Arm Description
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).
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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)
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.
Frequency of urolithiasis
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
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
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.
Full Information
NCT ID
NCT05443932
First Posted
March 15, 2022
Last Updated
October 19, 2023
Sponsor
Medical University of Vienna
1. Study Identification
Unique Protocol Identification Number
NCT05443932
Brief Title
Dapagliflozin and Hydrochlorothiazide in Recurring Kidney Stone Patients
Official Title
Dapagliflozin and Hydrochlorothiazide Treatment in Recurring Kidney Stone Patients - a Randomised Single Center Cross-over Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 4, 2024 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna
4. Oversight
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
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urolithiasis, Hyperoxaluria
Keywords
Urolithiasis, Hyperoxaluria
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Washout Phase and treatment arms
Arm Type
Other
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Intervention Description
10mg Dapagliflozin daily for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Hydrochlorothiazide
Intervention Description
50mg Hydrochlorothiazide daily for 8 weeks
Primary Outcome Measure Information:
Title
Δ of urinary oxalate excretion
Description
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)
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Δ of urinary calcium excretion
Description
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)
Time Frame
8 weeks
Title
Change of serum kreatinine
Description
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.
Time Frame
8 weeks
Title
Frequency of urolithiasis
Description
Frequency of sympothomatic or treatment worthy urolithiasis events within the 12 month lasting afterward study period. (in events/ person/ year)
Time Frame
12 months
Title
Tolerability of SGLT-2inhibitor therapy
Description
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)].
Time Frame
8 weeks
Title
Change of eGFR
Description
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.
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zeljko Kikic, Assoc.Prof.Priv.Doz.Dr
Phone
0043 (0)1 40400 43910
Email
zeljko.kikic@meduniwien.ac.at
Facility Information:
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
12. IPD Sharing Statement
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Dapagliflozin and Hydrochlorothiazide in Recurring Kidney Stone Patients
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