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

• 批准号: 10596711
• 负责人: Brendan Lee
• 金额: $ 33万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 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/10596711
• 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

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） 这是一个延续申请，以继续脆性骨病联盟的罕见疾病 临床研究网络（BBDC RDCRN）6-10年。BBDC专注于罕见的骨骼疾病 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、改变的生物材料性质如矿化和/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作用代表 不完美（OI）。虽然OI经常与BBD互换使用，但表型谱很快被改变。 扩张此外，了解这些表型的自然史是一个显著的未满足的需求 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脆骨 仍然是未知的，什么是适当的干预措施和各种疾病发病率的生物标志物是 开放性问题。在BBDC的第1-5年，我们在7个方案中的6个方案中达到或超过了应计目标。我们 已经发表或正在审查12篇描述我们的横截面数据的手稿。重要的是我们的 既往纵向研究、妊娠研究、颅面研究、试点胶原交联的结果 生物标志物研究和PROMIS试点研究已经授权设计和纳入新元素， 目前的纵向研究（项目1），正畸临床试验，以治疗咬合不正的OI（项目2），和 纵向生长生物标志物研究（项目3）。该BBDC将由12个临床研究中心组成， 美国和加拿大。BBDC的具体目标是：i）在以下方面进行合作临床研究： 包括上述三个临床项目在内的脆性骨疾病; ii）培训和吸引一批 临床骨研究的研究者将从本科生，学士后，研究生， 医学生、住院医师/研究员和初级教员;以及iii）与骨生成合作 * 不完美基金会（OIF）扩大培训材料工具箱，可用于广泛教育 患者、家庭和医疗保健提供者的广泛专业知识。