Cystinosis and Mitochondrial Metabolism

NCT07319091 | Not Yet Recruiting

• 1 other identifier: 69HCL25_0542
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 9

Brief Summary

Cystinosis is a monogenic autosomal recessive lysosomal storage disease with complete penetrance, caused by a biallelic mutation in the CTNS gene (17p13.2) encoding cystinosin, a ubiquitous membrane protein whose role is to clear cystine into the cytosol. Its dysfunction in patients with cystinosis leads to systemic accumulation of cystine, an oxidised dimer of cysteines linked by a disulphide bridge, in the lysosomal space, and irreversible cellular dysfunction. Renal damage is at the forefront, with Fanconi syndrome (proximal tubulopathy) and chronic renal failure developing early in childhood/adolescence. There are also multi-systemic disorders, notably endocrine and ophthalmological. Cysteamine is an amino thiol which reduces the level of intra-lysosomal cystine by breaking the disulphide strands of cystine, giving two cysteines which complex with cysteamine to leave the lysosome. Since the late 1980s, there has been an immediate-release form of the drug, which has considerably improved overall patient survival despite having a major impact on quality of life. This improvement in survival has also led to the emergence of later complications that were not previously observed. This musculoskeletal complication (described in an international consensus in 2019), known as 'CMBD' for Cystinosis Metabolic Bone Disease, may be explained at least in part by an intrinsic defect in the osteoblast and osteoclast that contribute to the human bone phenotype. This intrinsic bone defect appears to be responsible for premature ageing. In order to identify potential future therapeutic targets for CMBD, it is essential to gain a better understanding of the underlying pathophysiological mechanisms. To better understand premature aging in extra-renal damage in cystinosis, it seems relevant to investigate energy metabolism dysfunction, particularly mitochondrial dysfunction.

Conditions

Cystinosis; Native Kidney

Keywords

Cystinosis; Mitochondria; Cystinosis Metabolic Bone Disease (CMBD); Myopathy

Outcome Measures

Primary Outcomes (1)

• Membrane potential of circulating monocyte cells

  Mitochondrial metabolism was assessed by measuring the membrane potential by flow cytometry of circulating monocyte cells between subjects with and without cystinosis.

  24 months

Secondary Outcomes (22)

• Oxygen consumption rate (OCR) of circulating monocytic cells

  24 months

• Extracellular acidification rate (ECAR) of circulating monocytic cells

  24 months

• Age

  24 months

• Sex

  24 months

• Weight

  24 months

Study Arms (1)

Cystinosis patient

OTHER

Patient with genetically confirmed nephropathic cystinosis Men and women, children and adults with cystinosis Undergoing conservative treatment on native kidneys Age ≥ 2 years Patients receiving oral cysteamine Patients with social security coverage Informed consent signed by the participant or parents or legal guardians before participating in the study

Other: Mitochondrial metabolism

Interventions

Mitochondrial metabolism OTHER

Study of membrane potential by flow cytometry of circulating monocyte cells and evaluate the respiratory chain of these cells in patients with cystinosis and described musculoskeletal disorders in the study population in clinical and biological terms including metabolomic analysis of patients' blood and urine

Cystinosis patient

Eligibility Criteria

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

You may qualify if:

• Patient with genetically confirmed nephropathic cystinosis
• Men and women, children and adults with cystinosis
• Undergoing conservative treatment on native kidneys
• Age ≥ 2 years
• Patients receiving oral cysteamine
• Patients with social security coverage
• Informed consent signed by the participant or parents or legal guardians before participating in the study

You may not qualify if:

• Patient not complying with study procedures
• Transplant or dialysis patient
• Patient on anticalcineurin
• Pregnant or breast-feeding woman
• Person deprived of liberty by a judicial or administrative decision
• Person not affiliated to a social security scheme or beneficiaries of a similar scheme

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (9)

Service de néphrologie pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon

Bron, 69677 Bron Cedex, France

Location

Service de Néphrologie pédiatrique, Hôpital Jeanne de Flandre

Lille, 59000, France

Location

Service de néphrologie et exploration fonctionnelle rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon

Lyon, 69003, France

Location

Service de Néphrologie pédiatrique, Hôpital de la Timone

Marseille, 13385, France

Location

Service de Néphologie et endocrinologie pédiatrique, Hôpital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Service de Néphrologie pédiatrique, Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

Service de Néphrologie-transplantation rénale adultes, Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

Service de Néphrologie pédiatrique, Hôpital Robert Debré

Paris, 75019, France

Location

Service de Néphrologie-Dialyse-Transplantation pédiatrique, Hôpital d'enfants Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Cystinosis; Muscular Diseases

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Central Study Contacts

Justine BACCHETTA, MD

CONTACT

4 27 85 61 30; justine.bacchetta@chu-lyon.fr

Chloé GROSYEUX, MD

CONTACT

chloe.grosyeux@gmail.com

Study Design

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

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: January 6, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)