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

Primary Purpose

Cystinosis

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Cysteamine bitartrate
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Cystinosis focused on measuring Cystinosis, compliance, cysteamine, neurological assessments

Eligibility Criteria

4 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers
  • 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.

Sites / Locations

  • Hospices Civils de Lyon

Arms of the Study

Arm 1

Arm Type

No Intervention

Arm Label

Cysteamine Bitartrate

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Presence or absence and accountability of cystine crystals.
Eye examination
Memory and visuoperceptual tests repeated during the study
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.
NMRS assessments
Concentration of cysteamine in the CSF, associated to a measurement of the CSF pressure
concentration of cysteamine in blood (measured by toxicological HPLC analysis with fluorescence detection)
discrimination of urine and blood samples,from metabolic spectroscopic data obtained by nuclear magnetic resonance.
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.
pharmacokinetic profile and 2 timepoints pharmacodynamics.

Full Information

First Posted
December 11, 2012
Last Updated
May 4, 2022
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT02012114
Brief Title
A Cohort of Patients With Cystinosis : Compliance to Cysteamine and Neurological Complications
Acronym
Crystobs
Official Title
A Cohort of Patients With Cystinosis : Compliance to Cysteamine and Neurological Complications
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
December 5, 2016 (Actual)
Study Completion Date
December 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystinosis
Keywords
Cystinosis, compliance, cysteamine, neurological assessments

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cysteamine Bitartrate
Arm Type
No Intervention
Arm Description
Single arm study. Subjects receive their current oral form of cysteamine bitartrate treatment : Cystagon® or RP103
Intervention Type
Other
Intervention Name(s)
Cysteamine bitartrate
Intervention Description
No intervention
Primary Outcome Measure Information:
Title
WBC cystine levels
Description
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
Time Frame
Day1and every three months : Month1, Month3, Month6, Month9, Month12, Month15, Month18, Month21 and Month24.
Secondary Outcome Measure Information:
Title
Presence or absence and accountability of cystine crystals.
Description
Eye examination
Time Frame
Every 6 month : Month1, Month6, Month12, Month18, Month24
Title
Memory and visuoperceptual tests repeated during the study
Time Frame
at Day 1 and two years
Title
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.
Description
NMRS assessments
Time Frame
at Month 1 and two years
Title
Concentration of cysteamine in the CSF, associated to a measurement of the CSF pressure
Time Frame
at any visit
Title
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
Title
discrimination of urine and blood samples,from metabolic spectroscopic data obtained by nuclear magnetic resonance.
Description
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
Time Frame
Every 3 months during 6 months and every 6 months to month 6 until two years
Title
Concentration effect, dose effect model.
Description
pharmacokinetic profile and 2 timepoints pharmacodynamics.
Time Frame
at month 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cochat Pierre, PUPH
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Study Director
Facility Information:
Facility Name
Hospices Civils de Lyon
City
Lyon
ZIP/Postal Code
69002
Country
France

12. IPD Sharing Statement

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

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