The Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN)

全球脑白质营养不良倡议临床试验网络 (GLIA-CTN)

基本信息

批准号：
10704432
负责人：
FLORIAN S EICHLER
金额：
$ 13.77万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10704432
关键词：
Adrenomyeloneuropathy Adult Advocacy Advocate Affect Alexander Disease Ataxia Awareness Axon Bioinformatics Biological Markers Birth Blood Brain Caring Classification Clinical Clinical Trials Design Clinical Trials Network Collaborations Collection Communities Companions Computerized Medical Record Cost Sharing Data Diagnosis Disease Documentation Early Diagnosis Early identification Early treatment Epidemiologist Equilibrium Etiology Family Foundations Future Gait Gene Expression Glial Fibrillary Acidic Protein Health Expenditures Health Personnel Healthcare Hereditary Disease Individual Institution Interferons Joints Knowledge Leadership Longterm Follow-up Measurement Measures Membrane Lipids Metachromatic Leukodystrophy Methodology Mission Modeling Molecular Morbidity - disease rate Myelin Natural History Neonatal Screening Nervous system structure Outcome Pathway interactions Patient Outcomes Assessments Patient advocacy Patients Pelizaeus-Merzbacher Disease Performance Phase Pilot Projects Positioning Attribute Program Development Program Sustainability Publications Questionnaires Rare Diseases Recording of previous events Reproducibility Research Research Personnel Resources Scientist Severity of illness Signal Transduction Standardization Subgroup Surrogate Markers Syndrome System Technology Therapeutic Therapeutic Trials Time Training Translating base care burden career development clinical care clinical center clinical development clinical outcome assessment clinical research site clinical trial readiness data integration data sharing disease classification epidemiology study improved industry partner innovation leukodystrophy meetings next generation next generation sequencing novel patient advocacy group patient oriented preclinical development programs prospective pseudotoxoplasmosis syndrome rate of change remote assessment sharing platform tool wearable device white matter working group

Adrenomyeloneuropathy Adult Advocacy Advocate Affect Alexander Disease Ataxia Awareness Axon Bioinformatics Biological Markers Birth Blood Brain Caring Classification Clinical Clinical Trials Design Clinical Trials Network Collaborations Collection Communities Companions Computerized Medical Record Cost Sharing Data Diagnosis Disease Documentation Early Diagnosis Early identification Early treatment Epidemiologist Equilibrium Etiology Family Foundations Future Gait Gene Expression Glial Fibrillary Acidic Protein Health Expenditures Health Personnel Healthcare Hereditary Disease Individual Institution Interferons Joints Knowledge Leadership Longterm Follow-up Measurement Measures Membrane Lipids Metachromatic Leukodystrophy Methodology Mission Modeling Molecular Morbidity - disease rate Myelin Natural History Neonatal Screening Nervous system structure Outcome Pathway interactions Patient Outcomes Assessments Patient advocacy Patients Pelizaeus-Merzbacher Disease Performance Phase Pilot Projects Positioning Attribute Program Development Program Sustainability Publications Questionnaires Rare Diseases Recording of previous events Reproducibility Research Research Personnel Resources Scientist Severity of illness Signal Transduction Standardization Subgroup Surrogate Markers Syndrome System Technology Therapeutic Therapeutic Trials Time Training Translating base care burden career development clinical care clinical center clinical development clinical outcome assessment clinical research site clinical trial readiness data integration data sharing disease classification epidemiology study improved industry partner innovation leukodystrophy meetings next generation next generation sequencing novel patient advocacy group patient oriented preclinical development programs prospective pseudotoxoplasmosis syndrome rate of change remote assessment sharing platform tool wearable device white matter working group

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项目摘要

Abstract: Leukodystrophies are inherited diseases that affect the white matter of the brain due to the loss or absence of myelin, the lipid membrane that insulates axons in the nervous systems. The leukodystrophy community is at a key turning point. Novel molecular approaches have increased disease recognition. At the same time key disorders now have potential treatment pathways. There is urgent unmet need in clinical trial readiness, lest the promise in pre-clinical development be unable to be translated to well-designed clinical trials. This gap in knowledge has galvanized stakeholders in the disease community. In collaboration with advocacy partners, we have formed a research-based consortium, the Global Leukodystrophy InitiAtive Clinical Trials Network (GLIA-CTN). In this proposal, the GLIA-CTN will embark on a longitudinal natural history, focused on but not limited to five leukodystrophy with clinical trial readiness: Adrenomyeloneuropathy (AMN), Aicard Goutieres Syndrome (AGS), Alexander Disease (AxD), Metachromatic Leukodystrophy and Pelizaeus Merzbacher Disease. Approaches will include Clinical Outcome Assessments (COA) and Patient Reported Outcomes (PRO) with a focus on reliability, reproducibility and validity. Additionally, we will develop methodology around Electronic Medical Record (EMR) extraction of natural history data for the leukodystrophies. Companion projects around novel tools and scales to define the ataxia seen in AMN, novel disease classification strategies in AGS and their correlation with disease severity and biomarkers, and evidentiary criteria around GFAP (glial fibrillary acidic protein) as a biomarker for AxD complete the proposal. Oversight for these projects will occur under a well-developed Administrative Unit which includes a Data Integration Core staffed by bioinformatics, epidemiologists and biostatisticians thanks to significant cost sharing with participating institutions. Sustainability of the program is supplemented with a strong career development and pilot project program. All aspects of the program are carefully aligned with our patient advocacy partners who have provided meaningful input and will be stakeholders in data sharing platforms. Together, these approaches will establish a platform to develop clinical trial readiness across the leukodystrophies, in close partnership between clinician scientists, advocacy groups and industry partners, enabling transformation of the field.

抽象的：白细胞营养不良是遗传性疾病，由于损失或缺失而影响大脑的白质髓磷脂，可绝缘神经系统中轴突的脂质膜。白细胞病社区处于关键转折点。新颖的分子方法增加了疾病识别。同时关键疾病现在有潜在的治疗途径。临床试验准备就绪，避免了紧迫的需求，以免临床前发展的承诺无法转化为精心设计的临床试验。这个差距知识使疾病社区中的利益相关者激发了利益相关者。与倡导合作伙伴合作，我们已经形成了一个基于研究的财团，全球白细胞增强倡议临床试验网络（Glia-CTN）。在此提案中，胶质CTN将着重于纵向自然史，而不是限制五个白细胞营养不良，并具有临床试验准备：肾上腺瘤病（AMN），AICARD GOTIERES 综合征（AGS），亚历山大疾病（AXD），实质性白细胞营养不良和Pelizaeus Merzbacher 疾病。方法将包括临床结果评估（COA）和患者报告的结果（Pro）重点是可靠性，可重复性和有效性。此外，我们将围绕电子病历（EMR）提取白细胞营养不良的自然历史数据。伴侣围绕新颖的工具和秤的项目来定义AMN中发现的共济失调，新型疾病分类策略在AG中及其与疾病严重程度和生物标志物的相关性，以及GFAP周围的证据标准（Glial 作为AXD的生物标志物，原纤维酸性蛋白完成了该建议。这些项目将进行监督在一个发达的行政部门下，包括由生物信息学组成的数据集成核心，流行病学家和生物统计学家归功于与参与机构的大量成本共享。该计划的可持续性补充了强大的职业发展和试点项目计划。全部该计划的各个方面与我们的患者倡导伙伴仔细一致，他们提供了有意义的输入将是数据共享平台的利益相关者。这些方法将共同建立一个平台为了在临床医学家之间建立密切合作伙伴关系的整个白细胞病的临床试验准备就绪，倡导团体和行业合作伙伴，实现了该领域的转变。