Not Yet Recruiting

NCT Number: NCT07201701

Is CYP24A1 Heterozygosity a Risk Factor for Nephrolithiasis?

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

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

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

Age range

2 year–90 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Hôpital Femme Mère Enfant, Bron, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Supplementary blood samples for PBMC analysis at V2

Biological

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

Primary outcomes

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

Time frame: Visit 2 (at least 24 hours after baseline)

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

Study contacts

Contact information is provided by the study sponsor or research team.

Justine Pr BACCHETTA

CONTACT

[email protected]

0033427856178

Lydia SLIMANI

CONTACT

[email protected]

0033472681349

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Acronym: HETEROCYP

Important dates

Study start: 2025
Primary completion: 2026
Study completion: 2028
First posted: Oct 1, 2025
Registry last updated: Dec 2, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Recruiting