- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04874909
Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM) (CILLICORIRCM)
Classification and Functional Stratification of the Patients With Ciliopathy and Identification of Biomarkers to Improve Their Prognosis
The purpose of the C'IL-LICO RICM study is to develop innovative and transformative diagnostic and prognostic for patients suffering from ciliopathies leading to renal failure.
The objectives is to decipher disease mechanisms and highlight signaling pathways altered in at-risk to develop renal failure patient groups and to produce a prognostic biomarker-based kit to predict the evolution of ciliopathy patients towards renal impairment.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Ciliopathies are a large group of rare and severe genetic diseases caused by ciliary dysfunction, in which nearly all organs can be affected. In spite of being individually rare, they affect collectively up to one per 2000 people. Over the past two decades, more than 90 genes have been reported as mutated in ciliopathy patients. Most proteins encoded by these genes play key roles in the biogenesis or function of cilia, in which they define different functional subdomains. Genetic analyses of ciliopathies revealed a vast clinical variability and a broad genetic heterogeneity as: 1) mutations of the same disease-causing gene can result in distinct clinical entities and, conversely, 2) mutations in several independent genes can lead to similar clinical features, implying both phenotypic and genetic overlaps. The extent and severity of organ involvement may be correlated in part with the nature or location of the mutational event, the cell/tissue specific expression and effect of the mutated protein on cilia dysfunction.
Renal involvement is one of the most frequent manifestations in ciliopathies, and it leads to excessive morbidity and mortality. This includes renal cystic dysplasia (RCD), a kidney developmental defect, and nephronophthisis (NPHP), a chronic tubulointerstitial nephritis, both disorders representing frequent causes of end-stage renal disease (ESRD) during childhood to early adulthood. This makes ESRD a terminal endpoint of either isolated or syndromic ciliopathies, with, hitherto, no available curative treatment of chronic kidney disease whatsoever. The only bearable option is renal transplantation. As the average life-span of a functioning kidney transplant is about 10-15 years, it is urgent to identify therapeutic solutions that slow down progression of CKD in ciliopathies, and delay or avoid dialysis or transplantation. Today, the diagnosis of ciliopathies is first based on primary clinical manifestations, and then confirmed by gene mutation identification. However, even in patients with identified causative mutations, it is impossible to predict the severity of the disease, the risk of appearance (if not present at diagnosis), and/or the rate of progression of CKD. Thus, a crucial issue in the field of ciliopathies is to be able to perform early detection of at-risk patients prior to development of CKD as well as to predict disease progression rate.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Stanislas LYONNET, MD, PhD
- Phone Number: (33) 1 42 75 49 96
- Email: stanislas.lyonnet@aphp.fr
Study Locations
-
-
-
Paris, France, 75015
- Recruiting
- Hopital Necker-Enfants Malades
-
Contact:
- Stanislas LYONNET, MD, PhD
- Phone Number: (33) 1 42 75 49 96
- Email: stanislas.lyonnet@aphp.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
"Case" Patient :
- with nephronophthisis or ciliopathy with known genetic diagnosis or not
- signed the Informed consent form (patient or legal guardians if minor/incapable major)
- no limit of age, this patients could be recruited from the birth
- social insurance affiliation
Healthy related individual :
- related with a included patient (father, mother, brother, sister)
- signed the Informed consent form (major or legal guardians if minor/incapable major)
- no limit of age, this patients could be recruited from the birth
- social insurance affiliation
"Negative Control" patient :
- without chronic renal failure
- signed the Informed consent form (major or legal guardians if minor/incapable major)
- no limit of age, this patients could be recruited from the birth
- social insurance affiliation
"Positive Control" patient :
- with chronic renal failure not related with a ciliary dysfunction
- signed the Informed consent form (major or legal guardians if minor/incapable major)
- no limit of age, this patients could be recruited from the birth
- social insurance affiliation
Exclusion Criteria "Case" Patient :
- pregnant, parturious and nursing mothers.
- with functional renal graft
- use an experimental treatment during 30 days before inclusion date
Healthy related individual :
- pregnant, parturious and nursing mothers.
"Negative Control" patient :
- pregnant, parturious and nursing mothers.
"Positive Control" patient :
- pregnant, parturious and nursing mothers.
- with functional renal graft
- use an experimental treatment during 30 days before inclusion date
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: "Case" Patient
Patient with ciliopathy
|
Blood sample of 15ml max by subject (case, related individual, control) once time:
Urine sample (500 ml) once time
|
Other: Healthy related individual
Individual without ciliopathy but related to a patient with ciliopathy (father, mother, brother, sister)
|
Blood sample of 15ml max by subject (case, related individual, control) once time:
Urine sample (500 ml) once time
|
Other: "Negative Control" patient
patient without renal disease
|
Blood sample of 15ml max by subject (case, related individual, control) once time:
Urine sample (500 ml) once time
|
Other: "Positive Control" patient
patient with renal disease other that ciliopathy but with a similar renal function to the ciliopathy group ("case" patient)
|
Blood sample of 15ml max by subject (case, related individual, control) once time:
Urine sample (500 ml) once time
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in transcriptional profiles in different subtypes of ciliopathy patients and control subjects
Time Frame: 3 years
|
RNA-sequencing analysis will be utilized to identify changes in transcriptional profiles and biological pathways in subgroups of patients to research whether the target mutation gene combination analyzed by transcription group was consistent with clinical cell morphological diagnosis and disease progression. Different human models will be used: Urine-derived Renal Epithelial Cells (URECs), renal organoids from patients derived induced Pluripotent Stem Cells (iPSCs) and urines. |
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in proteome profiles in different subtypes of ciliopathy patients and control subjects
Time Frame: 3 years
|
Proteomics analysis will be utilized to identify changes in proteome profiles in subgroups of patients to research whether the target mutation gene combination analyzed by proteomics group was consistent with clinical cell morphological diagnosis and disease progression. Different human models will be used: Urine-derived Renal Epithelial Cells (URECs), renal organoids from patients derived induced Pluripotent Stem Cells (iPSCs) and urines. |
3 years
|
Change in metabolome profiles in different subtypes of ciliopathy patients and control subjects
Time Frame: 3 years
|
Metabolomics analysis will be utilized to identify changes in metabolome profiles in subgroups of patients to research whether the target mutation gene combination analyzed by metabolomics group was consistent with clinical cell morphological diagnosis and disease progression. Different human models will be used: Urine-derived Renal Epithelial Cells (URECs), renal organoids from patients derived induced Pluripotent Stem Cells (iPSCs) and urines. |
3 years
|
Collaborators and Investigators
Investigators
- Study Chair: Sophie SAUNIER, PhD, Imagine Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Eye Diseases
- Disease
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Hypothalamic Diseases
- Eye Diseases, Hereditary
- Abnormalities, Multiple
- Retinitis Pigmentosa
- Syndrome
- Bardet-Biedl Syndrome
- Laurence-Moon Syndrome
- Ciliopathies
Other Study ID Numbers
- APHP200896
- ID-RCB Number (Other Identifier: 2020-A02576-33)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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