A Cohort of Patients With Cystinosis : Compliance to Cysteamine and Neurological Complications

NCT02012114 | Completed DMC

• 1 other identifier: 2010-605
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Preventing late onset of Cystinosis such as neurological complications and improving compliance to cysteamine treatment remain major challenges in management of subjects with cystinosis. This study is designed to describe the relationship between compliance of patients with cystinosis treated with cysteamine and treatment efficacy and to understand the pathophysiologic mechanism of neurological disorders. Is cysteamine crossing the blood brain barrier? What is the impact of cystine accumulation in Cerebro Spinal Fluid and Central Nervous System? Our Primary objective is to study the relationship between compliance of patients treated with cysteamine and the WBC cystine level. Secondary, the study will assess relationship between compliance to cysteamine and its neurological consequences. The expected duration of the study is 48 months. The enrolment period is 24 months and the study participation of each subject is 24 months. Eligible participants are male and female (age \> 4 years) with confirmed diagnosis of cystinosis and receiving any oral cysteamine treatment: Cystagon or RP103. The compliance under cysteamine is measured using electronic devices, accountability of study treatment, and information in patients' diary. Specific memory and visuoperceptual tests are performed at the beginning and at the end of patients'participation. Nuclear Magnetic Resonance spectroscopy is used to detect possible sites of cystine accumulation in the CNS and their relationship with compliance to cysteamine treatment. NMRS is also used to establish a relationship with the neuropsychological status of the subject. To describe absorption, distribution and elimination of cysteamine, and its metabolic pathways, and to determine the concentration effect and dose effect relationship, blood samples are performed at each study visit. A lumbar puncture is also proposed to participants to verify if cysteamine is crossing the blood brain barrier. New tools are used to compare metabonomic networks in patients with cystinosis and their controls.

Conditions

Cystinosis

Keywords

Cystinosis, compliance, cysteamine, neurological assessments

Outcome Measures

Primary Outcomes (1)

• WBC cystine levels

  PD measurements will be performed at D1, M1, M3, M6, M9, M12, M15, M18, M21 and M24. Compliance under cysteamine will be measured from D1 to M24 using electronic devices (date and time of bottle opening are recorded), accountability of study treatment and information of patients' diary. Compliance measurement between two consecutive study visits will be expressed as the proportion of the observed number of opening compared to the expected number and the cumulated dose taken compared to the expected dose.Compliance will be first considered as a dichotomous variable, the compliance being described as satisfactory if greater than 95% during a specific period.Compliance will then be considered as a quantitative variable

  Day1and every three months : Month1, Month3, Month6, Month9, Month12, Month15, Month18, Month21 and Month24.

Secondary Outcomes (7)

• Presence or absence and accountability of cystine crystals.

  Every 6 month : Month1, Month6, Month12, Month18, Month24

• Memory and visuoperceptual tests repeated during the study

  at Day 1 and two years

• presence or absence of cystine accumulation, determination of the sites of cystine accumulation in the CNS and relationship with the compliance to cysteamine treatment, relationship with neuropsychological status.

  at Month 1 and two years

• Concentration of cysteamine in the CSF, associated to a measurement of the CSF pressure

  at any visit

• concentration of cysteamine in blood (measured by toxicological HPLC analysis with fluorescence detection)

  at Day1 and every 3 months : month1, month3, month6, month9, month12, month15, month18, month21, month24

Study Arms (1)

Cysteamine Bitartrate

NO INTERVENTION

Single arm study. Subjects receive their current oral form of cysteamine bitartrate treatment : Cystagon® or RP103

Other: Cysteamine bitartrate

Interventions

Cysteamine bitartrate OTHER

No intervention

Cysteamine Bitartrate

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• Subjects with known hypersensitivity to cysteamine and penicillamine.
• Females who are nursing, planning a pregnancy, known or suspected to be pregnant, or with a positive urinary pregnancy test.
• Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.
• Contra-indication to MRI assessment
• CONTROLS FOR METABONOMIC ASSESSMENTS
• \- Age and sex matched to study population: Age range: patients aged 4 to 5 years, 6 to 11 years, patients aged 12 to 17 years, adult patients: 18 or above.
• Sex: male or female
• Subjects or their parent or legal guardian must provide written informed consent prior to participation in the study.
• Subjects covered by or having the right to social security.
• \- Any uropathology or nephropathology.
• CONTROLS FOR NMRS ASSESSMENTS
• \- Age and sex matched to study population: Age range: patients aged 4 to 5 years, 6 to 11 years, patients aged 12 to 17 years, adult patients: 18 or above.
• Sex: male or female
• Subjects or their parent or legal guardian must provide written informed consent prior to participation in the study.
• Subjects covered by or having the right to social security.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hospices Civils de Lyon

Lyon, 69002, France

Location

Related Publications (1)

• Gaillard S, Roche L, Lemoine S, Deschenes G, Morin D, Vianey-Saban C, Acquaviva-Bourdain C, Ranchin B, Bacchetta J, Kassai B, Nony P, Bodenan E, Laudy V, Rouges C, Zarrabian S, Subtil F, Mercier C, Cochat P, Bertholet-Thomas A. Adherence to cysteamine in nephropathic cystinosis: A unique electronic monitoring experience for a better understanding. A prospective cohort study: CrYSTobs. Pediatr Nephrol. 2021 Mar;36(3):581-589. doi: 10.1007/s00467-020-04722-0. Epub 2020 Sep 9.

  PMID: 32901297 RESULT

MeSH Terms

Conditions

Cystinosis; Patient Compliance

Interventions

Cysteamine

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; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Mercaptoethylamines; Ethylamines; Amines; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds

Study Officials

• Cochat Pierre, PUPH

  Hospices Civils de Lyon

  STUDY DIRECTOR

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: December 11, 2012
• First Posted: December 16, 2013
• Study Start: December 1, 2011
• Primary Completion: December 5, 2016
• Study Completion: December 14, 2021
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

FR (1)