Status:
RECRUITING
Albuminuria Lowering Effect of Dapagliflozin, Spironolactone and Their Combination in Adult Patients with Alport Syndrome (COMBINE-ALPORT)
Lead Sponsor:
Stefan Lujinschi
Collaborating Sponsors:
Carol Davila University of Medicine and Pharmacy
Institutul Clinic Fundeni
Conditions:
Alport Syndrome
Thin Basement Membrane Disease
Eligibility:
All Genders
18-70 years
Phase:
PHASE4
Brief 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), t...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
February 26 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2026
Estimated Enrollment :
34 Patients enrolled
Trial Details
Trial ID
NCT06499948
Start Date
February 26 2024
End Date
March 1 2026
Last Update
July 15 2024
Active Locations (1)
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1
Fundeni Clinical Institute
Bucharest, Sector 2, Romania, 020021