A Cohort of Patients With Cystinosis : Compliance to Cysteamine and Neurological Complications
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 2
- 主要终点
- WBC cystine levels
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •- 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.
排除标准
- •- 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.
结局指标
主要结局
WBC cystine levels
时间窗: Day1and every three months : Month1, Month3, Month6, Month9, Month12, Month15, Month18, Month21 and Month24.
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
次要结局
- Concentration of cysteamine in the CSF, associated to a measurement of the CSF pressure(at any visit)
- Concentration effect, dose effect model.(at month 6)
- 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)
- 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)
- 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)
- discrimination of urine and blood samples,from metabolic spectroscopic data obtained by nuclear magnetic resonance.(Every 3 months during 6 months and every 6 months to month 6 until two years)