CompletedPhase 4

Albuminuria Lowering Effect of Dapagliflozin, Spironolactone and Their Combination in Adult Patients With Alport Syndrome (COMBINE-ALPORT)

Romania12 participantsStarted 2024-02-26

Plain-language summary

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).

Who can participate

Age range

18 Years – 70 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Genetically proven Alport syndrome (AS) - defined as following: * gt;Men having hemizygous pathogenic/likely pathogenic variants involving COL4A5 gene - classified as X-linked AS involving men * gt;Women having heterozygous pathogenic/likely pathogenic variants involving COL4A5 gene - classified as X-linked AS involving women * gt;Both men and women with heterozygous pathogenic/likely pathogenic variants involving COL4A3 or COL4A4 genes - classified as autosomal dominant AS * gt;Both men and women with homozygous pathogenic/likely pathogenic variants involving COL4A3 or COL4A4 genes - classified as autosomal recessive AS * gt;Patients having variants of uncertain significance will be included if the fulfill at least 2 of the following criteria: (1) clinical features suggestive of AS, (2) positive family history suggestive of AS (i.e., at least one grade I relative having the same variant and presenting clinical features suggestive of AS) and (3) kidney biopsy showing the characteristic lesion of AS (i.e., structural defect of the glomerular basement membrane, "basket-wave" appearance of the basement membrane, lamination of the basement membrane) or for thin basement membrane disease (i.e., diffusely thin basement membrane) * Age between 18 and 70 years-old at the time of enrolment * Baseline estimated glomerular filtration rate (eGFR) over 10ml/min/1.73m2 at the time of enrolment * Stable kidney function: variation of eGFR under 25% from base…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Change in 24-hours urine albumin-to-creatinine ratio (UACR) compared to baseline after treatment with Dapagliflozin, Spironolactone and with their combination

Timeframe: 24-hours UACR will be measured at 0, 2, 6, 10, 14, 18, 22, 26 and 30 weeks after eligibility assessment

Trial details

NCT IDNCT06499948

SponsorStefan Lujinschi

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-11-21

View on ClinicalTrials.gov More Alport Syndrome trials