Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies

NCT06648044 | Recruiting DMC

• 1 other identifier: IMIS2015-05
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

Brief Summary

Nephronophthisis (NPH) is an autosomal recessive, genetically heterogeneous disease, with mutations identified in over 20 genes (notably NPHP1 and NPHP4). These genetic defects are associated with reduced urine concentration, chronic tubulointerstitial nephritis, etc., and progress to end-stage renal failure before the age of 20. Nephronophthisis may occur as an isolated pathology, but is also often associated with various extrarenal symptoms. NPHP genes account for around 50% of the genes responsible for NPH. No effective treatment is available to date. Studying NPHP proteins and associated signaling pathways could help identify how to circumvent the problems of protein distribution and therapeutic mRNA, and could be applicable to a broad set of NPHP mutations. To this end, Dr. Saunier's laboratory at Institut Imagine has recently identified approved drugs that correct some of the ciliary and epithelial defects found in cells with NPHP mutations.

Conditions

Nephronophthisis; NPH1; Autosomal; Recessive; Genetically; Heterogenic; Disorder

Keywords

mutations; 20; genes

Outcome Measures

Primary Outcomes (1)

• Positive or negative confirmation of potential therapeutic targets in urine-derived renal epithelial cells of patients

  3 years

Secondary Outcomes (3)

• Experimental transcriptomics data package from in vitro tubule cell model perturbed with disease network modifying agents

  3 years

• A rank ordered list of specific druggable nodes within the NPHP disease module that could be targeted by biologic or chemical entities.

  3 years

• Identify biomarkers to evaluate the response to small molecules for the management of NPHP and other renal ciliopathies.

  3 years

Study Arms (4)

Patients with nephronophthisis/renal associated ciliopathies

OTHER

Affected patients: Suffering from nephronophthisis or renal associated ciliopathies with known genetic diagnosis or not, Having obtained the signature of the informed consent form of patient, parent Intervention : blood and urine sample collection Collection of urines from patients will be followed by multiomics analyses including proteome and miRNAome profiling on EVs purified from urines by ultracentrifugation and metabolomics on unfractionated urine. Biomarkers identification for ciliopathy-induced chronic kidney disease will allow to monitor the drug response in treated urine-derived renal epithelial cells.

Other: Description: Research of therapeutic targets in the frame of nephronophthisis and renal associated ciliopathie

Healthy relatives of Patients

OTHER

Healthy relatives: Being the healthy relative (father / mother / brother / sister) of an included patient Having signed the informed consent form (patient or parent in case of minor subject) No age limit is requested for these subjects, who can be recruited from birth. Intervention : blood and urine sample collection Collection of urines from patients will be followed by multiomics analyses including proteome and miRNAome profiling on EVs purified from urines by ultracentrifugation and metabolomics on unfractionated urine. Biomarkers identification for ciliopathy-induced chronic kidney disease will allow to monitor the drug response in treated urine-derived renal epithelial cells

Other: Description: Research of therapeutic targets in the frame of nephronophthisis and renal associated ciliopathie

Negative control

OTHER

Being unscathed of any chronic renal disease, with or without ciliopathies Having obtained the signature of the informed consent form No age limit is requested for these patients, who can be recruited from birth. Intervention : blood and urine sample collection Collection of urines from patients will be followed by multiomics analyses including proteome and miRNAome profiling on EVs purified from urines by ultracentrifugation and metabolomics on unfractionated urine. Biomarkers identification for ciliopathy-induced chronic kidney disease will allow to monitor the drug response in treated urine-derived renal epithelial cells

Other: Description: Research of therapeutic targets in the frame of nephronophthisis and renal associated ciliopathie

Positive control

OTHER

Suffering from Chronic Kidney Disease unrelated to ciliary dysfunction (such as glomerulopathy, tubulopathy…) Having obtained the signature of the informed consent form No age limit is requested for these patients, who can be recruited from birth. Intervention : blood and urine sample collection Collection of urines from patients will be followed by multiomics analyses including proteome and miRNAome profiling on EVs purified from urines by ultracentrifugation and metabolomics on unfractionated urine. Biomarkers identification for ciliopathy-induced chronic kidney disease will allow to monitor the drug response in treated urine-derived renal epithelial cells

Other: Description: Research of therapeutic targets in the frame of nephronophthisis and renal associated ciliopathie

Interventions

Description: Research of therapeutic targets in the frame of nephronophthisis and renal associated ciliopathie OTHER

Healthy relatives of Patients; Negative control; Patients with nephronophthisis/renal associated ciliopathies; Positive control

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be included in the protocol, subjects will have to respect the following criteria:
• Affected patients:
• Suffering from nephronophthisis or renal associated ciliopathies with known genetic diagnosis or not, Having obtained the signature of the informed consent form of patient, parent(s) or legal representative No age limit is requested for these patients, who can be recruited from birth.
• Healthy relatives:
• Being the healthy relative (father / mother / brother / sister) of an included patient Having signed the informed consent form (patient or parent in case of minor subject) No age limit is requested for these subjects, who can be recruited from birth.
• 'Negative' control patients: Being unscathed of any chronic renal disease, with or without ciliopathies Having obtained the signature of the informed consent form No age limit is requested for these patients, who can be recruited from birth.
• 'Positive' control patients Suffering from Chronic Kidney Disease unrelated to ciliary dysfunction (such as glomerulopathy, tubulopathy…) Having obtained the signature of the informed consent form No age limit is requested for these patients, who can be recruited from birth.

You may not qualify if:

• In order to be included in the protocol, subjects will have to fulfill none of the following criteria:
• Affected patients:
• Patients with a functioning kidney transplant (only for patient for who urine sample is performed. This criteria is not applicable when only blood is sampling) Patients included in a therapeutic protocol since fewer 30 days.
• Healthy relatives:
• 'Positive' control subjects: Patients with a functioning kidney transplant

Sponsors & Collaborators

• Imagine Institute: lead

Study Sites (1)

Imagine Institute

La Defense, France

RECRUITING

MeSH Terms

Conditions

Nephronophthisis, familial juvenile; Disease

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: October 18, 2024
• Study Start: February 1, 2016
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: September 5, 2025

Record last verified: 2025-08

Locations

FR (1)