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European Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome

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Brief Title † European Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome
Official Title † European Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome: Current and Novel Therapies
Brief Summary The hereditary type IV collagen disease Alport syndrome inevitably leads to end-stage renal disease. Currently there are no therapies known to improve outcome. Our non-interventional, observational study investigates, if medications such as ACE-inhibitors can (1) delay time to dialysis and (2) improve life-expectancy within three generations of Alport-families in Europe.
Detailed Description Early diagnosis in children with Alport syndrome (AS) with isolated hematuria opens a "window of opportunity" for early intervention. Currently there are no causal therapeutic options which are proven to delay renal failure in AS. ACE-inhibition (ACEi) has been shown to reduce proteinuria in Alport patients and to delay renal failure in Alport-mice suggesting it may be of value as an effective treatment to delay renal failure in humans. To test this we established the European Alport Registry to collect data over several generations of Alport families across Europe. Small children with AS first develop microscopic hematuria, proceeding to microalbuminuria, overt proteinuria, impaired renal function and end up with end stage renal disease. These different steps of disease enabled us to assess if earlier introduction of ACE-inhibition at earlier degrees of disease is more effective than later therapy in delaying the time to dialysis and improving life-expectancy. Heterozygous COL4A3/COL4A4 mutations result in the phenotype "familial benign hematuria" or "thin basement membrane nephropathy" (TBMN). Affected subjects typically present with hematuria. Having longtime been regarded as "benign" familial hematuria, those patients might have an increased risk to develop severe renal impairment - comparable to the findings in female XLAS carriers (see above). TBMN is not a rare disease, as at least 1% of the population is affected. For the first time, the present study compares the risk of renal impairment, end stage renal disease and premature death in between heterozygous carriers of XLAS and of ARAS mutations. Additionally, the nephroprotective effect of RAAS-blockade in patients with heterozygous Alport-mutations is evaluated.
Study Phase N/A
Study Type † Observational [Patient Registry]
Study Design † Observational Model: Cohort, Time Perspective: Cross-Sectional
Primary Outcome Measure † end stage renal disease
Secondary Outcome Measure † proteinuria after initiation of ACE-inhibitor-therapy
Condition † Alport Syndrome Hereditary Kidney Disease Pediatric Kidney Disease Thin Basement Membrane Disease Familial Benign Hematuria
Intervention † DrugACE-inhibitor
Study Arms / Comparison Groups no-T: untreated patients untreated patients, typically uncles or grandfathers of present patients. No Intervention (means no therapy until CKD stage V, on renal replacement therapy) T-III: late therapy in patients patients treated with RAAS-Blockade after onset of renal failure (GFR below 60 ml/min) (starts at patients with CKD stages III and IV). T-II: early therapy in patients therapy starts at patients with proteinuria >0.3 g/day or per gCreatinine T-I: very early tharpy in patients starts at patients with microhematuria only (usually at birth) or microalbuminuria (30-300 mg protein per day or per gCreatinine in children). no therapy in heterozygous carriers heterozygous carriers without therapy therapy in heterozygous carriers heterozygous carriers with RAAS-blockade
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 500
Start Date † July 1995
Completion Date July 2019
Primary Completion Date July 2010
Eligibility Criteria † Inclusion Criteria/ Exclusion Criteria: The diagnosis of Alport syndrome (AS) was proven by kidney biopsy or mutation analysis (or both). Patients were included if they were affected males with X-linked AS or patients with genetically proven homozygous autosomal AS. Patients were excluded if they did not give informed consent or the diagnosis was suspected but not confirmed. The diagnosis of the heterozygous status was proven by (1) mutation analysis or (2) kidney biopsy plus genetic consultation for decision in between XLAS or ARAS inheritance (including a conclusive genealogic tree and/or linkage analysis). Patients were excluded if they were affected males with XLAS or patients with genetically proven homozygous ARAS. Patients were excluded if they did not give informed consent or the diagnosis was suspected but not confirmed or if they donated a kidney (living donor to affected family member).
Gender Both
Ages N/A - N/A
Accepts Healthy Volunteers Accepts Healthy Volunteers
Contacts †† Oliver Gross, MD, +49-551-39-, gross.oliver@med.uni-goettingen.de
Location Countries † Germany
Administrative Information
NCT ID † NCT02378805
Organization ID Alport-UMG2010
Secondary IDs ††
Responsible Party Principal Investigator
Study Sponsor † University Hospital Goettingen
Collaborators †† Gesellschaft für Pädiatrische Nephrologie
Investigators † Principal Investigator: Oliver Gross, MD, University Hospital Goettingen
Information Provided By
Verification Date February 2015
First Received Date † February 26, 2015
Last Updated Date February 26, 2015
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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