Cystinosis and Mitochondrial Metabolism (CYSTI-MITO)

Evaluation of Mitochondrial Metabolism in Patients With Cystinosis: CYSTI-MITO Project

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cystinosis; Native Kidney
• Intervention / Treatment: Other: Mitochondrial metabolism

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Justine BACCHETTA, MD; Phone Number: +33 4 27 85 61 30; Email: justine.bacchetta@chu-lyon.fr
• Study Contact Backup: Name: Chloé GROSYEUX, MD; Email: chloe.grosyeux@gmail.com

Study Locations

• France
  • Bron, France, 69677 Bron Cedex
    • Service de néphrologie pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon
    • Contact: Justine BACCHETTA, MD; Phone Number: +33 4 27 85 61 30; Email: justine.bacchetta@chu-lyon.fr
    • Principal Investigator: Justine BACCHETTA, MD
    • Sub-Investigator: Chloé GROSYEUX, MD
    • Sub-Investigator: Aurélia BERTHOLET-THOMAS
  • Lille, France, 59000
    • Service de Néphrologie pédiatrique, Hôpital Jeanne de Flandre
    • Contact: Robert NOVO, MD
    • Principal Investigator: Robert NOVO, MD
  • Lyon, France, 69003
    • Service de néphrologie et exploration fonctionnelle rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon
    • Contact: Sandrine LEMOINE, MD
    • Principal Investigator: Sandrine LEMOINE, MD
  • Marseille, France, 13385
    • Service de Néphrologie pédiatrique, Hôpital de la Timone
    • Contact: Caroline ROUSSET-ROUVIERE, MD
    • Principal Investigator: Caroline ROUSSET-ROUVIERE, MD
  • Montpellier, France, 34295
    • Service de Néphologie et endocrinologie pédiatrique, Hôpital Arnaud de Villeneuve
    • Contact: Marc FILA, MD
    • Principal Investigator: Marc FILA, MD
  • Paris, France, 75015
    • Service de Néphrologie pédiatrique, Hôpital Necker-Enfants Malades
    • Contact: Olivia BOYER, MD
    • Principal Investigator: Olivia BOYER, MD
  • Paris, France, 75015
    • Service de Néphrologie-transplantation rénale adultes, Hôpital Necker-Enfants Malades
    • Contact: Aude SERVAIS, MD
    • Principal Investigator: Aude SERVAIS, MD
  • Paris, France, 75019
    • Service de Néphrologie pédiatrique, Hôpital Robert Debré
    • Contact: Julien HOGAN, MD
    • Principal Investigator: Julien HOGAN, MD
  • Vandœuvre-lès-Nancy, France, 54511
    • Service de Néphrologie-Dialyse-Transplantation pédiatrique, Hôpital d'enfants Brabois
    • Contact: Isabelle VRILLON, MD
    • Principal Investigator: Isabelle VRILLON, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cystinosis patient; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen consumption rate (OCR) of circulating monocytic cells	The oxygen consumption rate (OCR) of circulating monocytic cells is measured by the Seahorse method. This method also measures the extracellular acidification rate (ECAR) of cells. The oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) are used to assess the respiratory chain of the cells, which will be compared between subjects with and without cystinosis.	24 months
Extracellular acidification rate (ECAR) of circulating monocytic cells	The extracellular acidification rate (ECAR) of circulating monocytic cells is measured by the Seahorse method. This method also measures the oxygen consumption rate (OCR) of cells. The extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) are used to assess the respiratory chain of the cells, which will be compared between subjects with and without cystinosis.	24 months
Age	The patient's age is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : sex, weight, height, blood pressure, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire	24 months
Sex	The patient's sex is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, weight, height, blood pressure, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire	24 months
Weight	The patient's weight is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, height, blood pressure, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire	24 months
Height	The patient's height is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, blood pressure, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire	24 months
Blood pressure	The patient's blood pressure is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire	24 months
Type of treatment	The patient's type of treatment is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire	24 months
Bone deformity	The patient's bone deformity is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, treatment, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire	24 months
Clinical sign of myopathy	Clinical sign of myopathy is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, treatment, bone deformity, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire	24 months
Grip-test score	The Grip-test is used to assess grip strength. Grip-test score is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, treatment, bone deformity, clinical sign of myopathy and the EAT10 (Eating Assessment Tool) questionnaire	24 months
EAT10 (Eating Assessment Tool) questionnaire score	EAT10 (Eating Assessment Tool) questionnaire score is pathological if >= 3 : 3-10 mild dysphagia; 11-20 moderate dysphagia; 21-40 severe dysphagia) questionnaire. EAT10 score is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, treatment, bone deformity, clinical sign of myopathy and grip-test score	24 months
Complete ionogram	Complete ionogram is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as C-reactive protein (CRP), intra-leukocyte cystine, Parathyroid hormone (PTH), total alkaline phosphatases, 25(OH) vitamin D, 1-25 (OH) vitamin D	24 months
C-Reactive Protein (CRP)	C-Reactive Protein (CRP) is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, intra-leukocyte cystine, Parathyroid hormone (PTH), total alkaline phosphatases, 25(OH) vitamin D, 1-25 (OH) vitamin D	24 months
Intra-leukocyte cystine	Intra-leukocyte cystine is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP), Parathyroid hormone (PTH), total alkaline phosphatases, 25(OH) vitamin D, 1-25 (OH) vitamin D	24 months
Parathyroid hormone (PTH)	Parathyroid hormone (PTH) is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP),intra-leukocyte cystine, total alkaline phosphatases, 25(OH) vitamin D, 1-25 (OH) vitamin D	24 months
Total alkaline phosphatases	Total alkaline phosphatases is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP), intra-leukocyte cystine, Parathyroid hormone (PTH), 25(OH) vitamin D, 1-25 (OH) vitamin D	24 months
25(OH) vitamin D	25(OH) vitamin D is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP), intra-leukocyte cystine, Parathyroid hormone (PTH), total alkaline phosphatases, 1-25 (OH) vitamin D	24 months
1-25 (OH) vitamin D	1-25 (OH) vitamin D is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP), intra-leukocyte cystine, Parathyroid hormone (PTH), total alkaline phosphatases, 25 (OH) vitamin D	24 months
Distribution of plasma organic amino acids	Study of metabolomic analysis of patients' blood	24 months
Distribution of urinary organic amino acids	Study of metabolomic analysis of patients' urine	24 months
Urinary Krebs cycle intermediate metabolites	Study of metabolomic analysis of patients' urine	24 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: December 19, 2025
• First Posted (Actual): January 6, 2026

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Mitochondria; Myopathy; Cystinosis; Cystinosis Metabolic Bone Disease (CMBD)
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lysosomal Storage Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Muscular Diseases; Cystinosis
• Other Study ID Numbers: 69HCL25_0542

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No