Is CYP24A1 Heterozygosity a Risk Factor for Nephrolithiasis?

NCT07201701 | Not Yet Recruiting

• 2 other identifiers: 69HCL25_05072025-A01749-40
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

Biallelic loss-of-function variants in CYP24A1 have been identified as a common genetic cause of autosomal recessive hypercalcemia (ARH, ORPHA 300547, 1 in 80,000 live births), characterized by low PTH (parathyroid hormone) levels, a high 25-OH D/24,25-(OH)₂D ratio, and susceptibility to vitamin D intoxication. In humans, heterozygous pathogenic variants in CYP24A1 have been proposed both as responsible for an autosomal dominant disorder and as a risk factor for nephrolithiasis, but the rarity and heterogeneity of human data prevent a definitive answer to this crucial question. Nephrolithiasis is a complex disease in which nutritional factors - particularly sodium and protein intake (leading to hypercalciuria) - play a key role. It also has a heritability of 50%, suggesting the involvement of many genetic susceptibility factors, as well as monogenic forms (mainly autosomal recessive, but also dominant or X-linked), which have been identified in 10-20% of patients. The increasing prevalence of nephrolithiasis, affecting approximately 10% of the general population over a lifetime, has a significant financial impact on healthcare systems and imposes a major burden of morbidity, justifying further investigation into the genetic underpinnings of nephrolithiasis. The goal of the HeteroCYP project is to improve understanding of the phenotypes associated with heterozygous, compound heterozygous, and homozygous variants of CYP24A1 by comparing clinical and biological outcomes in patients according to their mutation type

Conditions

Nephrolithiasis

Keywords

CYP24A1 heterozygous; Nephrolithiasis; CYP24A1 homozygous, and compound heterozygous; Nephrocalcinosis

Outcome Measures

Primary Outcomes (1)

• Prevalence of nephrolithiasis in patients who are CYP24A1 heterozygous and homozygous (or compound heterozygous)

  Prevalence of nephrolithiasis (based on imaging) in patients who are CYP24A1

  Visit 2 (at least 24 hours after baseline)

Study Arms (2)

Patients carriers of a heterozygous CYP2A1 mutation

Patients carriers of a heterozygous CYP2A1 mutation with or without symptoms: history of nephrocalcinosis or nephrolithiasis

Biological: Supplementary blood samples for PBMC analysis at V2

Patients carriers of homozygous, and compound heterozygous CYP2A1 mutation

Patients carriers of homozygous, and compound heterozygous CYP2A1 mutation with or without symptoms: history of nephrocalcinosis or nephrolithiasis

Biological: Supplementary blood samples for PBMC analysis at V2

Interventions

Supplementary blood samples for PBMC analysis at V2 BIOLOGICAL

Supplementary blood (serum and plasma) and urines samples for bio collection at V3

Patients carriers of a heterozygous CYP2A1 mutation; Patients carriers of homozygous, and compound heterozygous CYP2A1 mutation

Eligibility Criteria

• Age: 2 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study focuses on patients who are CYP24A1 heterozygous, CYP24A1 homozygous, or compound heterozygous.

You may qualify if:

• Group 1: Heterozygous Patients
• Aged between 2 and 90 years
• Weight \> 12 kg
• Carriers of a heterozygous CYP24A1 mutation
• With or without symptoms: history of nephrocalcinosis or kidney stones
• Group 2: Homozygous / Compound Heterozygous Patients
• Aged between 2 and 90 years
• Weight \> 12 kg
• Carriers of a homozygous or compound heterozygous CYP24A1 mutation
• With or without symptoms: history of nephrocalcinosis or kidney stones

You may not qualify if:

• Individuals unable to collect 24-hour urine
• Individuals unable to be available for a full day in a day hospital (HDJ)
• Pregnant, postpartum, or breastfeeding women
• Individuals deprived of liberty by judicial or administrative decision
• Individuals receiving psychiatric care
• Individuals admitted to a healthcare or social institution for reasons other than participation in research
• Adults under legal protection (guardianship or trusteeship)
• Individuals not affiliated with a social security system or not benefiting from an equivalent scheme

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Hôpital Femme Mère Enfant

Bron, France

Location

Hôpital Edouard Herriot

Lyon, France

Location

MeSH Terms

Conditions

Nephrolithiasis; Nephrocalcinosis

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Male Urogenital Diseases; Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Justine Pr BACCHETTA

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Justine Pr BACCHETTA

CONTACT

0033427856178; Justine.bacchetta@chu-lyon.fr

Lydia SLIMANI

CONTACT

0033472681349; Sacha.flammier@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: October 1, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

FR (2)