BRITTLE BONE DISORDERS CONSORTIUM OF THE RARE DISEASE CLINICAL RESEARCH NETWORK

罕见疾病临床研究网络脆性骨疾病联盟

基本信息

批准号：
10478155
负责人：
Brendan Lee
金额：
$ 143.86万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-06 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10478155
关键词：
Advocacy American Anxiety Baltimore Biocompatible Materials Biological Markers Biostatistics Core Bone Diseases COL1A1 gene COL1A2 gene Canada Chicago Child Clinical Clinical Research Clinical Trials Collagen Collagen Gene Collagen Type I Communities Complement Complex Data Defect Dental Diagnostics Research Disease District of Columbia Educational workshop Elements Epiphysial cartilage Faculty Family Florida Foundations Genetic Heterogeneity Genetic Predisposition to Disease Genotype Goals Growth Health Personnel Health Sciences Hospitals Human Subject Research Hydroxylation Individual Infrastructure Institutes Institution Intervention Lead Longitudinal Studies Longitudinal observational study Los Angeles Malocclusion Manuscripts Measures Medical Medical Students Medical center Medicine Minerals Molecular Genetics Morbidity - disease rate Mutation National Institute of Dental and Craniofacial Research Natural History Nebraska New York Operative Surgical Procedures Oral health Oregon Orthodontic Osteoclasts Osteocytes Osteogenesis Imperfecta Pain interference Patient Care Patients Pediatric Hospitals Phenotype Physicians Pilot Projects Post-Translational Protein Processing Pregnancy Primary Care Physician Property Protocols documentation Publishing Randomized Rare Diseases Research Research Design Research Personnel Research Training Rotation Signaling Protein Societies Special Hospitals Structure Training United States National Institutes of Health Universities Wages Work base biomechanical engineering bone clinical heterogeneity clinical research site clinical trial readiness cohort college craniofacial crosslink data management design empowered meetings mineralization multidisciplinary open label osteoblast differentiation recruit research and development research study scoliosis spine bone structure tool trafficking undergraduate student web-based tool

项目摘要

PROJECT SUMMARY (OVERALL) This is a renewal application to continue the Brittle Bone Disorders Consortium of the Rare Diseases Clinical Research Network (BBDC RDCRN) for years 6-10. The BBDC is focused on rare bone diseases that are caused by defects in osteoblast differentiation and/or function which leads to qualitative and/or quantitative defects of bone, altered biomaterial properties such as mineralization, and/or downstream cellular changes in osteocytes and osteoclasts. These are represented by the different types of Osteogenesis Imperfecta (OI). While OI is often used interchangeably with BBD, the phenotypic spectrum is rapidly expanding. Moreover, there is a significant unmet need to understand the natural history of these phenotypes stratified by their molecular genetic etiologies. How these different mutations ultimately lead to brittle bone remains unknown and what are appropriate interventions and biomarkers of various disease morbidities are open questions. In years 1-5 of the BBDC, we met or exceeded accrual targets in 6 out of 7 protocols. We have published or have under review 12 manuscripts describing our cross sectional data. Importantly, our findings in the previous longitudinal study, pregnancy study, craniofacial study, pilot collagen crosslink biomarker study, and the PROMIS pilot study have empowered the design and inclusion of new elements in the current longitudinal study (Project 1), orthodontic clinical trial to treat malocclusion in OI (Project 2), and longitudinal biomarker study of growth (Project 3). This BBDC will be composed of 12 clinical sites covering the U.S. and Canada. The Specific Aims of the BBDC are: i) To perform collaborative clinical research in brittle bone disorders including the three clinical projects listed above; ii) To train and attract a cohort of investigators in clinical bone research who will be recruited from undergraduate, post-baccalaureate, graduate, medical student, resident/fellow, and junior faculty ranks; and iii) to collaborate with the Osteogenesis Imperfecta Foundation (OIF) to expand a tool box of training materials that can be used to broadly educate patients, families, and healthcare provider across a broad spectrum of expertise.

项目概要（总体）这是续签申请，旨在继续罕见疾病脆性骨疾病联盟临床研究网络 (BBDC RDCRN) 为期 6-10 年。 BBDC 专注于罕见骨病由成骨细胞分化和/或功能缺陷引起，导致定性和/或骨的定量缺陷、改变的生物材料特性（例如矿化）和/或下游细胞骨细胞和破骨细胞的变化。这些由不同类型的成骨代表不完美（OI）。虽然 OI 通常与 BBD 互换使用，但表型谱迅速变化扩大。此外，了解这些表型的自然历史的需求还没有得到满足根据其分子遗传病因进行分层。这些不同的突变如何最终导致骨质疏松仍然未知，各种疾病发病率的适当干预措施和生物标志物是什么开放式问题。在 BBDC 的第 1-5 年，我们在 7 个协议中的 6 个达到或超过了应计目标。我们已发表或正在审查 12 篇描述我们横截面数据的手稿。重要的是，我们的之前的纵向研究、妊娠研究、颅面研究、试点胶原蛋白交联的结果生物标志物研究和 PROMIS 试点研究使新元素的设计和纳入成为可能目前的纵向研究（项目 1）、治疗成骨不全咬合不正的正畸临床试验（项目 2），以及生长的纵向生物标志物研究（项目 3）。该BBDC将由12个临床中心组成，涵盖美国和加拿大。 BBDC 的具体目标是： i) 开展合作临床研究脆性骨疾病，包括上面列出的三个临床项目； ii) 培训和吸引一批临床骨研究的研究人员将从本科生、学士后、研究生、医学生、住院医师/研究员和初级教职人员； iii) 与 Osteogenesis 合作 Imperfecta 基金会 (OIF) 将扩展可用于广泛教育的培训材料工具箱患者、家庭和医疗保健提供者拥有广泛的专业知识。