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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Hospices Civils de Lyon
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT02012114
First received: December 11, 2012
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Cystinosis
Other: Cysteamine bitartrate

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Cohort of Patients With Cystinosis : Compliance to Cysteamine and Neurological Complications

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • WBC cystine levels [ Time Frame: Day1and every three months : Month1, Month3, Month6, Month9, Month12, Month15, Month18, Month21 and Month24. ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • Presence or absence and accountability of cystine crystals. [ Time Frame: Every 6 month : Month1, Month6, Month12, Month18, Month24 ] [ Designated as safety issue: No ]
    Eye examination

  • Memory and visuoperceptual tests repeated during the study [ Time Frame: at Day 1 and two years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: at Month 1 and two years ] [ Designated as safety issue: No ]
    NMRS assessments

  • Concentration of cysteamine in the CSF, associated to a measurement of the CSF pressure [ Time Frame: at any visit ] [ Designated as safety issue: No ]
  • concentration of cysteamine in blood (measured by toxicological HPLC analysis with fluorescence detection) [ Time Frame: at Day1 and every 3 months : month1, month3, month6, month9, month12, month15, month18, month21, month24 ] [ Designated as safety issue: No ]
  • discrimination of urine and blood samples,from metabolic spectroscopic data obtained by nuclear magnetic resonance. [ Time Frame: Every 3 months during 6 months and every 6 months to month 6 until two years ] [ Designated as safety issue: No ]
    Perturbed metabolic network resulting from the intake of cysteamine in comparison to controls,using urine and blood samples available for patients with cystinosis and their controls

  • Concentration effect, dose effect model. [ Time Frame: at month 6 ] [ Designated as safety issue: No ]
    pharmacokinetic profile and 2 timepoints pharmacodynamics.


Estimated Enrollment: 90
Study Start Date: December 2011
Estimated Study Completion Date: May 2015
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Cysteamine Bitartrate
Single arm study. Subjects receive their current oral form of cysteamine bitartrate treatment : Cystagon® or RP103
Other: Cysteamine bitartrate
No intervention

  Eligibility

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • Male and female subjects with confirmed diagnosis of nephropathic cystinosis (defined by clinical signs and WBC cystine level).
  • Age > 4 years.
  • Subjects receiving any oral cysteamine treatment: Cystagon or RP103.
  • Sexually active female subjects of childbearing potential must agree to utilize the same acceptable form of contraception from day 1 through completion of the study.
  • 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.

Exclusion Criteria:

  • 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

Inclusion Criteria:

- 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.

Exclusion Criteria:

- Any uropathology or nephropathology.

CONTROLS FOR NMRS ASSESSMENTS

Inclusion Criteria:

- 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.

Exclusion Criteria:

  • Any uropathology or nephropathology.
  • Any neurological and/or psychiatric disorder
  • Contra-indication to MRI assessment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02012114

Contacts
Contact: Pierre COCHAT, PU PH 04 27 85 61 25 pierre.cochat@chu-lyon.fr
Contact: Segolene GAILLARD 04 27 85 77 28 segolene.gaillard@chu-lyon.fr

Locations
France
Hospices Civils de Lyon Recruiting
Lyon, France, 69002
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Study Director: Cochat Pierre, PUPH Hospices Civils de Lyon
  More Information

No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT02012114     History of Changes
Other Study ID Numbers: 2010-605
Study First Received: December 11, 2012
Last Updated: December 10, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Hospices Civils de Lyon:
Cystinosis, compliance, cysteamine, neurological assessments

Additional relevant MeSH terms:
Cystinosis
Lysosomal Storage Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Cysteamine
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014