Cystinosis and Mitochondrial Metabolism
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Mitochondrial metabolism.
- Who it may be relevant to
- Registry conditions: Cystinosis, Native Kidney. Basic parameters: from 2 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Evaluation of Mitochondrial Metabolism in Patients With Cystinosis: CYSTI-MITO Project
Overview
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.
Interventions
- Other Mitochondrial metabolism
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
Primary outcome measures
- Membrane potential of circulating monocyte cells [Time frame: 24 months]
Secondary outcome measures (12)
- Oxygen consumption rate (OCR) of circulating monocytic cells [Time frame: 24 months]
- Extracellular acidification rate (ECAR) of circulating monocytic cells [Time frame: 24 months]
- Age [Time frame: 24 months]
- Sex [Time frame: 24 months]
- Weight [Time frame: 24 months]
- Height [Time frame: 24 months]
- Blood pressure [Time frame: 24 months]
- Type of treatment [Time frame: 24 months]
- Bone deformity [Time frame: 24 months]
- Clinical sign of myopathy [Time frame: 24 months]
- Grip-test score [Time frame: 24 months]
- EAT10 (Eating Assessment Tool) questionnaire score [Time frame: 24 months]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Other
Study locations
France · 9 centers
- Service de néphrologie pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon — Bron
- Service de Néphrologie pédiatrique, Hôpital Jeanne de Flandre — Lille
- Service de néphrologie et exploration fonctionnelle rénale, Hôpital Edouard Herriot, Hospi — Lyon
- Service de Néphrologie pédiatrique, Hôpital de la Timone — Marseille
- Service de Néphologie et endocrinologie pédiatrique, Hôpital Arnaud de Villeneuve — Montpellier
- Service de Néphrologie pédiatrique, Hôpital Necker-Enfants Malades — Paris
- Service de Néphrologie-transplantation rénale adultes, Hôpital Necker-Enfants Malades — Paris
- Service de Néphrologie pédiatrique, Hôpital Robert Debré — Paris
- … and 1 more center
Identifiers
NCT: NCT07319091 · 69HCL25_0542