A Phase 4 interventional study of Treatment with Spironolactone followed by Dapagliflozin followed by their combination and Treatment with Dapagliflozin followed by Spironolactone followed by their combination in Alport Syndrome, Thin Basement Membrane Disease and Alport Nephropathy, sponsored by Stefan Lujinschi. Completed at 1 site in Romania. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-06-25.
Sponsored by Stefan Lujinschi · Phase 4, Interventional, and Treatment
Alport syndrome (AS) is one of the most common monogenic kidney disorders, oftentimes leading to end-stage kidney disease (ESKD). As AS is caused by variants involving type IV collagen genes (COL4), there is no specific treatment aimed at stopping the disease progression. Large studies have validated the use of renin-angiotensin-system inhibitors (RASis) in AS, as these drugs can slow the progression to chronic kidney disease (CKD). These studies included mainly pediatric patients with X-linked AS (XLAS). There is a lack of data regarding the therapeutic approach in patients having autosomal dominant AS (ADAS).
Recent data from murine studies suggest that the combined therapy using a sodium-glucose-cotransporter 2 inhibitor (SGLT2i) and a mineralocorticoid receptor blocker (MRB) can reduce proteinuria in COL4A3 knock-out mice. The albuminuria lowering effect of this combination was demonstrated in other non-diabetic nephropathies. Used in monotherapy, both drugs have showed protective and antifibrotic effects in murine models of AS.
The COMBINE-ALPORT trial aims to evaluate the albuminuria lowering effect of Dapagliflozin, Spironolactone and their combination in adult patients with genetically proven AS when added to maximum tolerated RASi dose. As proteinuria is the primary driver of CKD progression, and the change in albuminuria is widely used as a surrogate endpoint for kidney disease progression, lowering albuminuria will delay the onset of ESKD in patients with AS.
The main hypothesis of COMBINE-ALPORT trial is that the association of Dapagliflozin and Spironolactone will significantly reduce albuminuria in adult patient with AS.
The patients will be randomized to receive either Spironolactone or Dapagliflozin on top of standard therapy (maximum RASi dose) in a cross-over trial design (4 weeks of treatment followed by 4 weeks of wash-out). Finally, the whole cohort will receive both Spironolactone and Dapagliflozin for another 4 weeks.
The patients will visit the clinic every 4 weeks for checkups and tests.
The primary outcome is the effect on albuminuria by each treatment regimen (Spironolactone, Dapagliflozin or their combination).
38 studies on the registry are indexed under Nephritis, Hereditary; 14 are open to participants now.
This study's enrollment of 12 is below the median of 50 across 21 interventional studies indexed under Nephritis, Hereditary.
Browse Nephritis, Hereditary studies →Stefan Lujinschi is the lead sponsor of 3 studies on the registry; 2 are open to participants now.
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Genetically proven Alport syndrome (AS) - defined as following:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The patients will be randomized to receive either Spironolactone or Dapagliflozin on top of standard therapy (stable doses of renin-angiotensin-system inhibitors) in a crossover trial design (4 weeks of treatment followed by 4 weeks of wash-out). Finally, the whole cohort will receive both Spironolactone and Dapagliflozin for another 4 weeks. Treatment succession no.1 description: (1)1st treatment period - patients will receive Spironolactone 25 mg od on top of standard for 4 weeks; (2) 1st washout-period - treatment with Spironolactone will be stopped for 4 weeks; (3) 2nd treatment period - patients will receive Dapagliflozin 10 mg od for 4 weeks; (4) 2nd washout-period - treatment with Dapagliflozin will be stopped for 4 weeks; (5) 3rd treatment period - patients will receive Spironolactone 25 mg od plus Dapagliflozin 10 mg od for 4 weeks; (6) 3rd washout-period - treatment with Spironolactone and Dapagliflozin will be stopped for 4 weeks.
Drug: Treatment with Spironolactone followed by Dapagliflozin followed by their combination
The patients will be randomized to receive either Spironolactone or Dapagliflozin on top of standard therapy (stable doses of renin-angiotensin-system inhibitors) in a crossover trial design (4 weeks of treatment followed by 4 weeks of wash-out). Finally, the whole cohort will receive both Spironolactone and Dapagliflozin for another 4 weeks. Treatment succession no.2 description: (1) 1st treatment period - patients will receive Dapagliflozin 10 mg od on top of standard for 4 weeks; (2) 1st washout-period - treatment with Dapagliflozin will be stopped for 4 weeks; (3) 2nd treatment period - patients will receive Spironolactone 25 mg od for 4 weeks; (4) 2nd washout-period - treatment with Spironolactone will be stopped for 4 weeks; (5) 3rd treatment period - patients will receive Spironolactone 25 mg od plus Dapagliflozin 10 mg od for 4 weeks; (6) 3rd washout-period - treatment with Spironolactone and Dapagliflozin will be stopped for 4 weeks.
Drug: Treatment with Dapagliflozin followed by Spironolactone followed by their combination
Drug pages: Spironolactone · Dapagliflozin
After titrating the renin-angiotensin-system inhibitor dose, patients will receive 25 mg of Spironolactone once daily for 4 weeks. Spironolactone will be stopped after 4 weeks. The first treatment period will be followed by 4 weeks of wash-out. After the first wash-out period, treatment with Dapagliflozin will be started. Patients will receive 10 mg of Dapagliflozin once daily for 4 weeks. Dapagliflozin will be stopped after 4 weeks. The second treatment period will be followed by 4 weeks of wash-out. After the second wash-out period, treatment with both Spironolactone 25 mg and Dapagliflozin will be started. Patients will receive 25 mg of Spironolactone once daily in combination with 10 mg of Dapagliflozin daily for a duration of 4 weeks. Spironolactone and Dapagliflozin will be stopped after 4 weeks. The third treatment period will be followed by 4 weeks of wash-out, after which the study will be finalized.
Also known as: Treatment succession no. 1, Spironolactone-Dapagliflozin-Combination, SDC succession, Spironolactone first
Drug pages: Dapagliflozin · Spironolactone
After titrating the renin-angiotensin-system inhibitor dose, patients will receive 10 mg of Dapagliflozin once daily for 4 weeks. Dapagliflozin will be stopped after 4 weeks. The first treatment period will be followed by 4 weeks of wash-out. After the first wash-out period, treatment with Spironolactone will be started. Patients will receive 25 mg of Spironolactone once daily for 4 weeks. Spironolactone will be stopped after 4 weeks. The second treatment period will be followed by 4 weeks of wash-out. After the second wash-out period, treatment with both Spironolactone and Dapagliflozin will be started. Patients will receive 25 mg of Spironolactone once daily in combination with 10 mg of Dapagliflozin daily for a duration of 4 weeks. Spironolactone and Dapagliflozin will be stopped after 4 weeks. The third treatment period will be followed by 4 weeks of wash-out, after which the study will be finalized.
Also known as: Treatment succession no. 2, Dapagliflozin-Spironolactone-Combination, DSC succession, Dapagliflozin first
Change in 24-hours urine albumin-to-creatinine ratio (UACR) compared to baseline after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: 24-hours UACR will be measured at 0, 2, 6, 10, 14, 18, 22, 26 and 30 weeks after eligibility assessment
Change in estimated glomerular filtration ratio (eGFR) compared to baseline after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: eGFR will be measured at 0, 2, 6, 10, 14, 18, 22, 26 and 30 weeks after eligibility assessment
Change in serum potassium compared to baseline after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: Serum K will be measured at 0, 2, 6, 10, 14, 18, 22, 26 and 30 weeks after eligibility assessment
The occurrence of adverse events, including serious adverse events
Time frame: During and after each period of treatment, up to 24 weeks after randomization (30 weeks after assessing eligibility)
Change in urinary electrolytes excretion (sodium and potassium) compared to baseline after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: Urinary sodium and potassium will me measured each 4 weeks up to 24 weeks after randomization: before and after each period of treatment and wash-out
Reduction of 24-hours UACR with more than 30% from baseline after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: Change of UACR will be asses after each period of treatment (at 4, 12 and 20 weeks after randomization)
Reduction of 24-hours UACR with more than 50% from after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: Change of UACR will be asses after each period of treatment (at 4, 12 and 20 weeks after randomization)
Reduction of eGFR with more than 30% from baseline after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: Change in eGFR will be asses after each period of treatment (at 4, 12 and 20 weeks after randomization)
Reduction of eGFR with more than 50% from baseline and/or doubling serum creatinine and/or initiation of kidney replacement therapy after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: Change in eGFR will be asses after each period of treatment (at 4, 12 and 20 weeks after randomization)
Increase in serum potassium over 5.5 mmol/l and with more than 15% compared to baseline after treatment with Dapagliflozin, Spironolactone and with their combination
Time frame: Changes in serum K will be assessed after each period of treatment (4, 12 and 20 weeks after randomization)
Plan to share: Undecided
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This study is completed, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Spironolactone · Dapagliflozin