Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 2 for:    Ramipril | Alport Syndrome

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02378805
Recruitment Status : Recruiting
First Posted : March 4, 2015
Last Update Posted : March 24, 2020
Sponsor:
Collaborators:
Society for Pediatric Nephrology (Germany)
Deutsche Gesellschaft für Nephrologie
Alport Selbsthilfe e.V.
Association pour l'Information et la Recherche sur les Maladies Rénales Génétiques (AIRG)
KfH Foundation Preventive Medicine
Information provided by (Responsible Party):
Prof. Dr. O. Gross, University Hospital Goettingen

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.

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

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.

Layout table for study information
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

Resource links provided by the National Library of Medicine

Drug Information available for: Ramipril

Group/Cohort Intervention/treatment
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).
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!

T-II: early therapy in patients
therapy starts at patients with proteinuria >0.3 g/day or per gCreatinine
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!

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).
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!

no therapy in heterozygous carriers
heterozygous carriers without therapy
therapy in heterozygous carriers
heterozygous carriers with RAAS-blockade
Drug: ACE-inhibitor
observational study!
Other Name: Ramipril

Drug: AT1-inhibitor
observational study!

Drug: HMG-Coenzyme inhibitor (statin)
observational study!

Drug: Spironolactone
observational study!




Primary Outcome Measures :
  1. end stage renal disease [ Time Frame: unlimited ]
    Age at onset of end stage renal failure

  2. life-expectancy [ Time Frame: unlimited ]
    life-expectancy of patients and carriers


Secondary Outcome Measures :
  1. proteinuria after initiation of ACE-inhibitor-therapy [ Time Frame: unlimited ]
  2. proportion of patients with a clinical diagnosis of hypertension [ Time Frame: unlimited ]
  3. 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
Urine and serum-samples.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

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.

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).


Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Oliver Gross, MD +49-551-39- ext 6331 gross.oliver@med.uni-goettingen.de

Locations
Layout table for location information
Germany
University Hospital Goettingen Recruiting
Goettingen, Germany, 37075
Contact: Oliver Gross, MD    +49-551-39- ext 8912    gross.oliver@med.uni-goettingen.de   
Sponsors and Collaborators
University Hospital Goettingen
Society for Pediatric Nephrology (Germany)
Deutsche Gesellschaft für Nephrologie
Alport Selbsthilfe e.V.
Association pour l'Information et la Recherche sur les Maladies Rénales Génétiques (AIRG)
KfH Foundation Preventive Medicine
Investigators
Layout table for investigator information
Principal Investigator: Oliver Gross, MD University Hospital Goettingen
Additional Information:

Publications of Results:

Layout table for additonal information
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: March 24, 2020
Last Verified: March 2020
Keywords provided by Prof. Dr. O. Gross, University Hospital Goettingen:
Alport syndrome
thin basement membrane disease
familial benign hematuria
Additional relevant MeSH terms:
Layout table for MeSH terms
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
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