SLC13A5 Deficiency: a Prospective Natural History Study - Remote Only (International)
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Seizure burden and semiology
研究概览
简要总结
SLC13A5 deficiency (Citrate Transporter Disorder, EIEE 25) is a rare genetic disorder with neurodevelopmental delays and seizure onset in the first few days of life. This natural history study is designed to address the lack of understanding of disease progression and genotype-phenotype correlation. Additionally it will help in identifying clinical endpoints for use in future clinical trials.
详细描述
This is a longitudinal observational study for the natural history of SLC13A5 deficiency for up to 2 years. This study does not involve any therapeutic intervention. The study includes remote visits which will be done via telephone or remote video conferencing. Translators will be available during these remote visits for non-english speaking caregivers. The initial visit will consist of collecting a detailed medical history and medical records. Prior brain imaging and available EEGs will be collected and reviewed by the study neurologist. Neuropsychological assessments will be made using Vineland Adaptive Behavior Scale version 3. Brief standardized videos recorded by the caregiver will be reviewed and scored by study personnel for movement assessment. Caregiver of ages 2 and up will be asked to complete the QOL Family Impact Module and the QOL epilepsy module. In addition to the initial visit, assessments in 1st year (every 3 months) and 2nd year (every 4 months) of enrollment will be made through remote interviews. Caregiver will be asked to maintain a seizure diary for the duration of the study to assess seizure burden. Personnel having expertise to comprehensively evaluate biological pathways that are perturbed by SLC13A5 deficiency will analyze the collected data. Improved understanding of disease pathogenesis will guide therapeutics and reveal clinical endpoints for use in future clinical trials. Identifying genotype-phenotype correlations can guide prognostication, clinical management, and genetic counseling.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parent(s)/legal representative and/or patient must be willing and able to give informed consent/assent for participation in the study.
- •Males and females of any age are eligible for this study
- •Suspected or confirmed diagnosis of SLC13A5 deficiency with genetic variants in both SLC13A5 alleles and consistent clinical characteristics. Variants of uncertain significance in one or both alleles are acceptable if deemed good candidates by participant's primary geneticist or neurologist and study personnel.
- •Participant and caregiver must be willing to provide clinical data and participate in standardized assessments.
排除标准
- •The presence of a second, confirmed disorder, genetic or otherwise, affecting neurodevelopment or with other overlapping symptoms of SLC13A5 deficiency.
结局指标
主要结局
Seizure burden and semiology
时间窗: Upto 24 months
Caregiver will be asked to log number and type of seizures for the 4 weeks prior to each remote interview in a seizure tracker form. Reportable seizure types are to include: simple partial seizures (focal onset with retained awareness) WITHOUT motor signs, simple partial seizures WITH motor signs, complex partial seizures (focal onset with impaired awareness), partial (focal) seizures with secondary generalization, absences, myoclonic seizures, clonic seizures, tonic seizures, atonic seizures, and generalized tonic-clonic seizures. In addition, to assess overall change in seizure burden in 4 months between the remote interviews, Seizure Global Impression of Change (Seizure GIC) will be filled at all the remote interviews. Caregiver global impression of change will be assessed using a seven-point Likert scale. In addition, caregiver impression of change in seizure frequency and duration will be assessed using a three-point Likert scale.
SLC13A5 deficiency motor scale assessments.
时间窗: Upto 24 months
Caregiver will be asked to record brief standardized videos capturing the degree of disordered movements. These videos will be made and reviewed for all assessment sessions. Different movements/tasks will be assessed on different scales ranging from 0 to 8. Lesser scores represent better outcome.
Developmental assessment at baseline and longitudinally using Vineland 3
时间窗: Upto 24 months
The Vineland Adaptive Behavior Scales, Third Edition (Vineland 3) provides a comprehensive assessment of adaptive function and has been widely used in populations with intellectual and developmental disabilities. It is validated from birth to 90 years, and scores abilities across three core and two optional domains: communication, daily living skills, socialization, and motor skills and maladaptive behaviors, respectively. Completion time for the comprehensive interview is estimated at 50 minutes when all five domains are included. Reliability and validity are widely established. Vineland 3 Adaptive Behavior Scale questionnaire will be included in the remote interviews during the initial visit for baseline assessment and followed at 6 months, 12 months and 24 months for longitudinal neuropsychological assessment
次要结局
- Sleep disturbances scale for children (SDSC)(Upto 24 months)
- Caregiver Quality of Life (QOL)(Upto 24 months)