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Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM) (CILLICORIRCM)

Primary Purpose

Ciliopathies, Nephronophthisis, Senior-Loken Syndrome

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Blood sample
Urine sample
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Ciliopathies focused on measuring Ciliopathies, Pediatrics, Genetic diseases, Chronic Kidney Disease, Biomarkers

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpital Necker-Enfants MaladesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

"Case" Patient

Healthy related individual

"Negative Control" patient

"Positive Control" patient

Arm Description

Patient with ciliopathy

Individual without ciliopathy but related to a patient with ciliopathy (father, mother, brother, sister)

patient without renal disease

patient with renal disease other that ciliopathy but with a similar renal function to the ciliopathy group ("case" patient)

Outcomes

Primary Outcome Measures

Change in transcriptional profiles in different subtypes of ciliopathy patients and control subjects
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.

Secondary Outcome Measures

Change in proteome profiles in different subtypes of ciliopathy patients and control subjects
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.
Change in metabolome profiles in different subtypes of ciliopathy patients and control subjects
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.

Full Information

First Posted
March 31, 2021
Last Updated
October 28, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT04874909
Brief Title
Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
Acronym
CILLICORIRCM
Official Title
Classification and Functional Stratification of the Patients With Ciliopathy and Identification of Biomarkers to Improve Their Prognosis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 8, 2021 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ciliopathies, Nephronophthisis, Senior-Loken Syndrome, Joubert Syndrome, Jeune Syndrome, Bardet-Biedl Syndrome
Keywords
Ciliopathies, Pediatrics, Genetic diseases, Chronic Kidney Disease, Biomarkers

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
"Case" Patient
Arm Type
Other
Arm Description
Patient with ciliopathy
Arm Title
Healthy related individual
Arm Type
Other
Arm Description
Individual without ciliopathy but related to a patient with ciliopathy (father, mother, brother, sister)
Arm Title
"Negative Control" patient
Arm Type
Other
Arm Description
patient without renal disease
Arm Title
"Positive Control" patient
Arm Type
Other
Arm Description
patient with renal disease other that ciliopathy but with a similar renal function to the ciliopathy group ("case" patient)
Intervention Type
Other
Intervention Name(s)
Blood sample
Intervention Description
Blood sample of 15ml max by subject (case, related individual, control) once time: subject less than 5 kg : 1.8 to 4.5 ml max subject 5 kg to 10 kg : 4.5 to 9 ml max subject 10 kg to 15 kg : 9 to 13.5 ml subject 15 kg to 20 kg : 13.5 to 15 ml max
Intervention Type
Other
Intervention Name(s)
Urine sample
Intervention Description
Urine sample (500 ml) once time
Primary Outcome Measure Information:
Title
Change in transcriptional profiles in different subtypes of ciliopathy patients and control subjects
Description
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Change in proteome profiles in different subtypes of ciliopathy patients and control subjects
Description
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.
Time Frame
3 years
Title
Change in metabolome profiles in different subtypes of ciliopathy patients and control subjects
Description
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.
Time Frame
3 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stanislas LYONNET, MD, PhD
Phone
(33) 1 42 75 49 96
Email
stanislas.lyonnet@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Sandra COLAS
Phone
+33 1 71 19 64 32
Email
sandra.colas@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sophie SAUNIER, PhD
Organizational Affiliation
Imagine Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Hôpital Necker-Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stanislas LYONNET, MD, PhD
Phone
(33) 1 42 75 49 96
Email
stanislas.lyonnet@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)

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