Cystinosis and Mitochondrial Metabolism

Официальное название

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

Обзор

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.

Вмешательства

• Другое 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

Первичные конечные точки

• Membrane potential of circulating monocyte cells [Срок оценки: 24 months]

Вторичные конечные точки (12)

• Oxygen consumption rate (OCR) of circulating monocytic cells [Срок оценки: 24 months]
• Extracellular acidification rate (ECAR) of circulating monocytic cells [Срок оценки: 24 months]
• Age [Срок оценки: 24 months]
• Sex [Срок оценки: 24 months]
• Weight [Срок оценки: 24 months]
• Height [Срок оценки: 24 months]
• Blood pressure [Срок оценки: 24 months]
• Type of treatment [Срок оценки: 24 months]
• Bone deformity [Срок оценки: 24 months]
• Clinical sign of myopathy [Срок оценки: 24 months]
• Grip-test score [Срок оценки: 24 months]
• EAT10 (Eating Assessment Tool) questionnaire score [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Франция · 9 центров

• 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
• … и ещё 1 центр

Идентификаторы

NCT: NCT07319091 · 69HCL25_0542

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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