Eurbio-Alport (RaDiCo Cohort) (RaDiCo Eurbio-Alport) (Eurbio-Alport)

Study of the Natural History of Alport Syndrome by Establishment of an International Database

Alport syndrome is a rare, inherited condition characterized by a combination of glomerular nephropathy progressing to kidney failure, deafness, and eye involvement. This disease is associated with mutations in the genes encoding one of the three IV collagen chains expressed in the glomerular basement membrane. Significant progress has been made in understanding the molecular mechanisms responsible for the disease, but relatively little in understanding the progression of renal failure and in the area of therapeutics. We have shown in a retrospective European study that blockers of the renin angiotensin system may slow disease progression, but no controlled studies have been performed. Finally, innovative therapies (anti-micro-RNA, stem cells) have recently shown their effectiveness in animal models of the disease, and industrials are planning to quickly carry out phase 1 trials to test molecules. Carrying out therapeutic trials in humans will require full knowledge of the natural history of the disease (isolated hematuria, microalbuminuria, macroalbuminuria, renal failure and its progression) and gathering a sufficient number of patients, especially in the early stages. These trials and the indications for treatments would be greatly facilitated by the discovery of biomarkers that make it possible to predict the progression to renal failure earlier than the onset of proteinuria.

The study aims to:

• Establish a European database on Alport syndrome to assess the natural history of the disease.
• To investigate the impact of the disease on the educational and professional life of patients and their families, and on the adherence and tolerance to renin-angiotensin system blockers prescribed to proteinuric patients.
• Investigate access to molecular diagnostics and genetic counseling, as well as identify biomarkers that can predict progression of kidney disease.

This project will be carried out at a French level with the support and participation of the very active renal rare disease sector, in collaboration with various countries wishing to participate.

Study Overview

• Status: Recruiting
• Conditions: Alport Syndrome

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Laurence Heidet, PHD; Phone Number: 0033 1 44 49 43 82; Email: laurence.heidet@aphp.fr
• Study Contact Backup: Name: Bertrand Knebelmann, PHD; Email: bertrand.knebelmann@aphp.fr

Study Locations

• France
  • Île-de-France
    • Paris, Île-de-France, France, 75012
      • Recruiting
      • RaDiCo Eurbio-Alport
      • Contact: Sonia Gueguen, PHD; Phone Number: 0033 6 88 34 54 08; Email: sonia.gueguen@radico.fr
      • Principal Investigator: Laurence Heidet, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The countries that are potentially interested in joining the project have identified in their local records about 100 (Germany), 200 (Spain), 100 (United Kingdom), 785 (Italy), 100 (Belgium) patients. The database ASTOR in USA have included 800 patients. For France, the CEMARA database contains currently 680 Alport Syndrome patients while there are 950 identified patients in France. These patients are followed in nephrology and paediatric nephrology services belonging to the French network for rare renal diseases. Prevalent cases will include cases already registered in the different existing databases in the different countries, after monitoring that the inclusion criteria are respected. There is no known estimated incident rate, but according to the available information and the estimated prevalence rate (1/5,000), it is expected to enrol roughly between 100 and 200 incident patients/year in the study.

Description

Inclusion Criteria:

• Diagnosis of AS based on electron microscopic examination of the renal biopsy and/or molecular studies and/or abnormal expression of type IV collagen chains on skin and/or glomerular basement membranes.
• Signed informed consent

Exclusion Criteria:

- No exclusion criteria

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Renal function: eGFR, age at ESRD, requirement of Renal Replacement Therapy (RRT) and type of RRT	Through study completion, at 1 year, 2 year, 3 year
Urine bio-analysis results: Presence or not and quantification of hematuria, microalbuminuria and proteinuria	Through study completion, at 1 year, 2 year, 3 year
Presence or not of hypertension	Through study completion, at 1 year, 2 year, 3 year
Level of Hearing loss	Through study completion, at 1 year, 2 year, 3 year
Ocular symptoms (presence or not of lenticonus, cataract, retina and cornea impairment)	Through study completion, at 1 year, 2 year, 3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events for the long-term safety of RAAS blockers treatment		Through study completion, at 1 year, 2 year, 3 year
Quality of life questionnaires	Impact of disease on quality of life will be evaluated through scores of quality of life questionnaires SF36 for Adult et SF10 for paediatric patients	Through study completion, at 1 year, 2 year, 3 year
Compliance	Compliance will be evaluated using X. Girerd Compliance Questionnaire	Throughout the follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease stage	Stratification of patients according to their disease stage; patients' distribution analysis among countries	Throughout the follow-up
Urinal concentration of specific molecules	Correlation assessment between the urinal concentration of the five molecules recently described by Terzi's lab as predicting progression of CKD (or other putative biomarkers) with the rate of decline of the GFR (according of the estimated GFR) on a 3 year- period	Through study completion, at 1 year, 2 year, 3 year

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Laurence Heidet, PHD, INSERM U933

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2017
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: June 22, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 22, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Quality of life; Kidney disease; Rare disease; Alport Syndrome; Predictive biomarkers; Molecular diagnostics; European database
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Urogenital Abnormalities; Congenital Abnormalities; Connective Tissue Diseases; Nephritis; Collagen Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Nephritis, Hereditary
• Other Study ID Numbers: C15-82

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No