Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 6
- 主要终点
- Survival (Infantile GM1 population)
研究概览
简要总结
Owing to the rarity, severity, speed of progression and fatal prognosis of infantile and juvenile GM1, there is a limited understanding of overall disease progression and meaningful outcome measures. This study aims to build a natural history data set through collection of a number of clinical, imaging, and laboratory assessments that may be specific predictors of GM1 disease progression and clinical outcome. Having a GM1 natural history data set can inform potential efficacy endpoints and biomarkers for future clinical trials.
This natural history study will follow up to 40 subjects diagnosed with GM1 gangliosidosis (up to 20 infantile (Type 1) and 20 late infantile/juvenile (Type 2)) for up to 3 years. Visits will be conducted every 6 months, during which several procedures will be performed and the data recorded in order to learn about the natural course of the disease, including changes in clinical and neurological assessments and electrophysiologic, imaging and biofluid biomarkers. Study procedures include: physical & neurological exam, blood & urine sample collection, questionnaires & assessments of development, seizure diary, ECHO, ECG, x-ray and ultrasound (if MRI not performed), EEG and genetic testing (if not already done).
The following procedures are subject to local/institutional policies and the medical discretion of the Study Physician: MRI, lumbar puncture (spinal tap) and General anesthesia/sedation (for MRI and LP).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documentation/ Confirmation of reduced beta-galactosidase enzyme activity in leukocytes
- •Confirmed diagnosis of infantile or juvenile GM1 gangliosidosis with documentation of GLB1 mutations
- •Parent/Caregiver capable of providing informed consent (if cognitively able, child to provide assent as well)
- •Infantile (Type 1) GM1 subjects: Documented symptom onset by 6 months of age with significant hypotonia on exam or history elicited from parent(s)/ caregiver(s)
- •Juvenile (Type 2) GM1 subjects: Documented symptom onset after 6 months of age OR documented symptom onset prior to 6 months of age without significant hypotonia on exam or elicited from parent(s)/ caregiver(s)
排除标准
- •Enrollment in any other clinical study with an investigational product/ therapy (patients receiving miglustat off-label will be eligible)
- •Any clinically significant neurocognitive deficit not attributable to GM1 gangliosidosis or a secondary cause that may, in the opinion of the investigator, confound interpretation of study results
- •Any condition that, in the opinion of the investigator, would put the subject at undue risk or make it unsafe for the subject to participate
结局指标
主要结局
Survival (Infantile GM1 population)
时间窗: Baseline through 36 months (3 years)
Survival will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.
Change from baseline in standard scores for each domain on the Vineland-II (Juvenile GM1 population)
时间窗: Baseline through 36 months (3 years)
The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) is a standard assessment for measuring personal and social skills for children and adults (birth through 90 years of age). This assessment aids in diagnosis of intellectual and developmental disabilities or delays associated with a variety of diseases/disorders. The assessment includes 5 domains. Scores for each domain and a composite adaptive behavior score are then converted to standard scores with a range of 20 to 140, with a score of 140 correlating to a high adaptive level.
Presence of and dependence on feeding tube (Infantile GM1 population)
时间窗: Baseline through 36 months (3 years)
The presence of a feeding tube and dependence on the feeding tube, if applicable, will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.
Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Juvenile GM1 population)
时间窗: Baseline through 36 months (3 years)
Based on the outcome of the Vineland-II, each subject will be given a developmental age score that will determine whether the Bayley Scale of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II) is administered. Children with a developmental age of 42 months or less will be administered the BSID-III and those with a developmental age of greater than 42 months will be administered the KABC-II. The BSID-III assesses 5 major areas of development. Each domain results in a raw score that is converted to a composite score. A higher composite score generally corresponds with higher function. The KABC-II assesses 4 major areas of intelligence and achievement in young children. Each domain results in a raw score that is converted to a standard score. Scores from 90-109 are generally considered average, with scores higher than 109 considered to be above average.
次要结局
- Change from baseline EEG(Baseline through 36 months (3 years))
- Change from baseline in the PedsQL total score(Baseline through 36 months (3 years))
- Survival (Juvenile GM1 population)(Baseline through 36 months (3 years))
- Presence of and dependence on feeding tube (Juvenile GM1 population)(Baseline through 36 months (3 years))
- Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Infantile GM1 population)(Baseline through 36 months (3 years))
- Change from baseline ECG(Baseline through 36 months (3 years))
- Change from baseline in bony structures of the spine using X-ray(Baseline through 36 months (3 years))
- Change from baseline in brain volume and volume of substructures measured using MRI(Baseline through 36 months (3 years))
- Change from baseline in liver and spleen volume measured using MRI(Baseline through 36 months (3 years))
- Change from baseline in attainment and/or retention of six World Health Organization motor development milestones(Baseline through 36 months (3 years))
- Onset of and/or change in seizure activity over time(Baseline through 36 months (3 years))
- Change from baseline in ECHO parameters over time(Baseline through 36 months (3 years))
- Change from baseline in liver and spleen volume measured using ultrasound(Baseline through 36 months (3 years))