SLC13A5 Deficiency: A Prospective Natural History Study - United States Only
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 17
- 试验地点
- 3
- 主要终点
- Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: dental evaluations
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. Additionally it will identify clinical and biomarker endpoints for use in future clinical trials.
详细描述
This is a longitudinal observational study of the natural history of SLC13A5 deficiency for up to 2 years. This study does not involve any therapeutic intervention. The study includes in-person clinical assessments and laboratory analyses including standardized clinical evaluations, neurocognitive and quality of life scales, video movement rating scale, laboratory measurements of blood and urine, EEG capturing wake and sleep, EKG. Additionally, remote assessments in 1st year (every 3 months) and 2nd year (every 4 months) of enrollment will be made and caregiver will be asked to keep a seizure diary for the duration of the study. 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 and biomarker endpoints for use in future clinical trials.
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 SLC135 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, participate in standardized assessments, and provide biological samples.
- •Willingness to travel to one of the three sites annually is favored, but not required.
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
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: dental evaluations
时间窗: Up to 24 months
Conducted in patients with SLC13A5 deficiency: baseline pain assessment from a scale of 0-10 (0 being no pain and 10 being highest pain), temperature pain assessment for cold from a scale of 0-10 (0 being no pain and 10 being highest pain), temperate pain assessment for hot from a scale of 0-10 (0 being no pain and 10 being highest pain), toothpaste use (type and frequency), and Fluoride treatments. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: vitals and biometrics evaluations
时间窗: Up to 24 months
Conducted in patients with SLC13A5 deficiency: height (cm), weight (kg), blood pressure (systolic and diastolic), temperature (c), heart rate (beats/minute), respiratory rate (breaths/minute), and head circumference (cm). As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Neurodevelopmental profile of SLC13A5 deficiency as measured using the Peabody Developmental Motor Scales-2
时间窗: Up to 24 months
Six subtests that measure motor ability in children: reflexes, stationary, locomotion, object manipulation, grasping, and visual motor integration. The Peabody has quotients that measure a child's motor ability: gross motor quotient, fine motor quotient, total motor quotient. This is based on child's age and there are no higher or lower scores that indicate a better or worse outcome. Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: clinical and research laboratory studies
时间窗: Up to 24 months
Conducted in patients with SLC13A5 deficiency: Clinical: ammonia, amylase, CKMB, GGT, lactate, lipase, PT/PTT, vitamin d 25-oh, CBC with differential, comprehensive MET panel, lipid panel with calculated LDL, and urine studies (calcium/creatinine ratio, spot ph, spot citrate concentration, citrate/creatinine ratio). Research: Citrate and metabolomics. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: neurologic evaluation
时间窗: Up to 24 months
Conducted in patients with SLC13A5 deficiency: motor, motor stability, muscle bulk, paresis, sensation, reflexes, coordination, gait, and autonomic. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: scoring of movement disorder and SLC13A5 deficiency symptom scales
时间窗: Up to 24 months
Conducted in patients with SLC13A5 deficiency: using scale titled "Movement Exam for SLC13A5 Natural History Study". Assessing typical gait, standing in natural position, sitting on chair, head control, attempt to vocalize, speech quality, speech content, ability to grab items, and ability to draw. Symptom scales consist of chorea, dystonia, ataxia, myoclonus, tremor, hypokinetic-rigid syndrome, and tic. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: general evaluations
时间窗: Up to 24 months
Conducted in patients with SLC13A5 deficiency: general appearance, HEENT, neck, chest and lungs, cardiovascular, abdomen, genitourinary, rectal, musculoskeletal, lymph nodes, extremities/skin, mental status (alertness, interaction, language (EXP) (REC)), emotional affect (calm, smiling, laughing, anxious, frowning, crying, irritable, screaming). As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: electroencephalogram (EEG)
时间窗: Up to 24 months
Conducted in patients with SLC13A5 deficiency: looking at the duration of EEG, if they are captured awake or asleep, and if it is abnormal. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Neurodevelopmental profile of SLC13A5 deficiency as measured using Mullen Scales of Early Learning
时间窗: Up to 24 months
Consists of a gross-motor scale and four cognitive scales: visual reception, fine motor, receptive language, and expressive language. T-Scores (mean of 50 and a standard deviation of 10) are given for individual scales, and an optional Early Learning Composite standard score (mean of 100 and a standard deviation of 15) serves as an overall estimate of cognitive functioning. This is based on child's age and there are no higher or lower scores that indicate a better or worse outcome. Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
Neurodevelopmental profile of SLC13A5 deficiency as measured using the Vineland-III Adaptive Behavior Scale
时间窗: Up to 24 months
Vineland is a semi-structured interview that assesses adaptive behavior in several domains, summarized by the Adaptive Behavior Composite (ABC) standard score. ABC standard scores may range from 20 to 160, with a population mean of 100 and a standard deviation of 15. There are no higher or lower scores that indicate a better or worse outcome. Developmental assessment at baseline and longitudinally, if age and ability-appropriate. Additionally, Vineland-III Adaptive Behavior Scale questionnaire will be included in the remote assessment interview.
Seizure burden and semiology as measured using the Seizure Global Impression of Change
时间窗: Up to 24 months
Assessing the status of the patient's overall condition using a scale ranging from very much improved, much improved, slightly improved, no change, slightly worse, much worse, very much worse. Assessing the average number of participants' seizures on a scale of decreased, stayed the same, increased. Assessing the average duration of the participants' seizures on a scale of decreased, stayed the same, increased. Caregiver will be asked to maintain a seizure diary throughout the study and seizure burden will be assessed at in-person and remote assessments.
次要结局
- Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Family Impact(Up to 24 months)
- Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Caregiver Epilepsy Module(Up to 24 months)
- Participant sleep disturbances as measured through the Sleep Disturbances Scale for Children (SDSC)(Up to 24 months)