European Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome
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| ClinicalTrials.gov Identifier: NCT02378805 |
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Recruitment Status :
Recruiting
First Posted : March 4, 2015
Last Update Posted : May 24, 2022
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| Condition or disease | Intervention/treatment |
|---|---|
| Alport Syndrome Hereditary Kidney Disease Pediatric Kidney Disease Thin Basement Membrane Disease Familial Benign Hematuria | Drug: ACE-inhibitor Drug: AT1-inhibitor Drug: HMG-Coenzyme inhibitor (statin) Drug: Spironolactone Drug: Paricalcitol Drug: SGLT2 inhibitor |
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 Type : | Observational [Patient Registry] |
| Estimated Enrollment : | 500 participants |
| Observational Model: | Cohort |
| Time Perspective: | Cross-Sectional |
| Target Follow-Up Duration: | 10 Years |
| Official Title: | European Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome: Current and Novel Therapies |
| Study Start Date : | July 1995 |
| Actual Primary Completion Date : | July 2010 |
| Estimated Study Completion Date : | January 2035 |
| Group/Cohort | Intervention/treatment |
|---|---|
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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)
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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).
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Drug: ACE-inhibitor
observational study!
Other Name: Ramipril Drug: AT1-inhibitor observational study! Drug: HMG-Coenzyme inhibitor (statin) observational study! Drug: Spironolactone observational study! Drug: Paricalcitol observational study! Drug: SGLT2 inhibitor observational study! |
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T-II: early therapy in patients
therapy starts at patients with proteinuria >0.3 g/day or per gCreatinine
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Drug: ACE-inhibitor
observational study!
Other Name: Ramipril Drug: AT1-inhibitor observational study! Drug: HMG-Coenzyme inhibitor (statin) observational study! Drug: Spironolactone observational study! Drug: Paricalcitol observational study! Drug: SGLT2 inhibitor observational study! |
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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).
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Drug: ACE-inhibitor
observational study!
Other Name: Ramipril Drug: AT1-inhibitor observational study! Drug: HMG-Coenzyme inhibitor (statin) observational study! Drug: Spironolactone observational study! Drug: Paricalcitol observational study! |
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no therapy in heterozygous carriers
heterozygous carriers without therapy
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therapy in heterozygous carriers
heterozygous carriers with RAAS-blockade
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Drug: ACE-inhibitor
observational study!
Other Name: Ramipril Drug: AT1-inhibitor observational study! Drug: HMG-Coenzyme inhibitor (statin) observational study! Drug: Spironolactone observational study! Drug: SGLT2 inhibitor observational study! |
- end stage renal disease [ Time Frame: unlimited ]Age at onset of end stage renal failure
- life-expectancy [ Time Frame: unlimited ]life-expectancy of patients and carriers
- proteinuria after initiation of ACE-inhibitor-therapy [ Time Frame: unlimited ]
- proportion of patients with a clinical diagnosis of hypertension [ Time Frame: unlimited ]
- proportion of patients experiencing side effects from ACE-inhibitors [ Time Frame: unlimited ]defined as acute renal failure (doubling of serum-creatinine), angioedema, hyperkalemia >5.0 mmol/l, dry cough, symptomatic hypotension (orthostatic collapse) and others, and death from all causes.
Biospecimen Retention: Samples Without DNA
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
Currently there are no causal therapeutic options which are proven to delay renal failure in AS. We established the European Alport Registry to collect data over several generations of Alport families across Europe. The 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).
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.
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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02378805
| Contact: Oliver Gross, MD | +49-551-39- ext 6331 | gross.oliver@med.uni-goettingen.de |
| Germany | |
| University Hospital Goettingen | Recruiting |
| Goettingen, Germany, 37075 | |
| Contact: Oliver Gross, MD +49-551-39- ext 8912 gross.oliver@med.uni-goettingen.de | |
| Principal Investigator: | Oliver Gross, MD | University Hospital Goettingen |
Publications of Results:
Other Publications:
| Responsible Party: | Prof. Dr. O. Gross, Prof. Dr. Oliver Gross, University Hospital Goettingen |
| ClinicalTrials.gov Identifier: | NCT02378805 |
| Other Study ID Numbers: |
Alport-UMG2010 |
| First Posted: | March 4, 2015 Key Record Dates |
| Last Update Posted: | May 24, 2022 |
| Last Verified: | May 2022 |
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Alport syndrome thin basement membrane disease familial benign hematuria |
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Syndrome Ramipril Kidney Diseases Renal Insufficiency Hematuria Nephritis, Hereditary Disease Pathologic Processes Urologic Diseases Urination Disorders Hemorrhage Urogenital Abnormalities Nephritis Congenital Abnormalities Collagen Diseases |
Connective Tissue Diseases Sodium-Glucose Transporter 2 Inhibitors Spironolactone Angiotensin-Converting Enzyme Inhibitors Mineralocorticoid Receptor Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Diuretics, Potassium Sparing Diuretics Natriuretic Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antihypertensive Agents |