Effect of Dapagliflozin and Spironolactone on Kidney Health in Alport Syndrome
A Unicentric, Randomized, Open-label, Cross-over Clinical Trial to Assess the Effect of Dapagliflozin, Spironolactone and Their Combination, When Added to Renin-Angiotensin System Blockade, on Lowering Urine Albumin-to-Creatinine Ratio in Adult Patients with Alport Syndrome
This study is testing if the medications Dapagliflozin and Spironolactone can help adults with Alport Syndrome reduce protein in their urine and slow down kidney damage.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 34 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | Institutul Clinic Fundeni Academic / other |
| Locations | 1 site (Bucharest, Sector 2) |
| Trial ID | NCT06499948 on ClinicalTrials.gov |
What this trial studies
This study investigates the effects of Dapagliflozin, Spironolactone, and their combination on reducing albuminuria in adult patients with Alport Syndrome, a genetic kidney disorder. The trial aims to evaluate the efficacy of these medications, which have shown promise in other kidney conditions, in slowing disease progression. Participants will receive treatments in various sequences to assess the best therapeutic approach. The study focuses on both X-linked and autosomal forms of Alport Syndrome, addressing a gap in existing research.
Who should consider this trial
Good fit: Ideal candidates include adults with genetically confirmed Alport Syndrome, including both X-linked and autosomal variants.
Not a fit: Patients without a confirmed genetic diagnosis of Alport Syndrome or those with other unrelated kidney conditions may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could provide a new therapeutic option to slow the progression of kidney disease in patients with Alport Syndrome.
How similar studies have performed: Previous studies have shown success with similar therapeutic approaches in other nephropathies, but this specific combination in Alport Syndrome is novel.
Eligibility criteria
Show full inclusion / exclusion criteria
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 baseline in the last 6 weeks before randomization * 24-hours urine albumin-to-creatinine ratio greater than 30 mg/g after adjusting the dose of renin-angiotensin-system inhibitor * Stable renin-angiotensin-system inhibitor dose for at least 2 weeks before randomization Exclusion Criteria: * The need for kidney replacement therapy (i.e., hemodialysis, peritoneal dialysis, and kidney transplant) for more than 4 weeks in the last 12 months before enrollment * Treatment with Spironolactone or Dapagliflozin for more than 14 days in the last 28 days prior to enrollment * History of prior serious adverse event due to Spironolactone or Dapagliflozin * Active neoplasia * Autosomal dominant or recessive polycystic kidney disease * Type I diabetes * Patients with type II diabetes and diabetic nephropathy * Diagnosis of another concomitant distinct glomerulopathy (with the exception of concomitant IgA nephropathy on kidney biopsy) * Pregnancy and breastfeeding * History of solid organ transplant * Immunosuppressive treatment in the last 12 weeks prior to enrollment
Where this trial is running
Bucharest, Sector 2
- Fundeni Clinical Institute — Bucharest, Sector 2, Romania (Recruiting)
Study contacts
- Study coordinator: Ștefan N Lujinschi, MD, PhD candidate
- Email: stefanlujinschi@gmail.com
- Phone: +40728102643
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.