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: 9118704
• 负责人: Brendan Lee
• 金额: $ 126.15万
• 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 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9118704
• 关键词: Adult; Advocacy; Affect; Antibodies; Baltimore; Biochemistry; Biological Markers; Biometry; Bone Diseases; Boxing; Canada; Chicago; Child; Childhood; Clinical; Clinical Research; Clinical Treatment; Collagen; Collagen Gene; Collagen Type I; Complex; Data; Deformity; Dental; Development; Diagnosis; Diagnostics Research; Disease; District of Columbia; Dose; E-learning; Educational workshop; Epidemiology; Faculty; Family; Fellowship; Florida; Foundations; Fracture; Gender; Genes; Genetic Predisposition to Disease; Genotype; Health Personnel; Health Sciences; Hereditary Disease; Heterogeneity; Hospitals; Human; Human Subject Research; Hydroxylation; Industry; Information Systems; Institutes; Knowledge; Lead; Life; Link; Los Angeles; Mass Spectrum Analysis; Measurement; Measures; Medical; Medical Genetics; Medical Students; Medical center; Medicine; Molecular Genetics; Mutation; Natural History; New York; New York City; Observational Study; Operative Surgical Procedures; Oregon; Osteogenesis Imperfecta; Outcome; Patient Outcomes Assessments; Patient advocacy; Patients; Pattern; Phase; Phenotype; Physicians; Pilot Projects; Post-Translational Protein Processing; Pregnancy; Primary Health Care; Principal Investigator; Race; Rare Diseases; Recruitment Activity; Research; Research Personnel; Research Training; Resources; Rotation; Severities; Severity of illness; Signal Pathway; Signal Transduction; Signaling Protein; Site; Special Hospitals; Spinal Fractures; Structure; System; Testing; Therapeutic; Training; Translating; Universities; Wages; Washington; base; biomechanical engineering; bone; burden of illness; chronic pain; clinical research site; cohort; college; control trial; craniofacial; crosslink; design; disease natural history; member; mouse model; multidisciplinary; novel; novel marker; phase I trial; preclinical study; public health relevance; research study; response; scoliosis; skeletal; success; therapeutic target; tool; trafficking; urinary

DESCRIPTION (provided by applicant): This is an application to establish a Brittle Bones Disorders Rare Disease Clinical Research Consortium (BBD RDCRC) focused on studying the over 13 genetic conditions that not contribute to the Osteogenesis Imperfecta (OI) phenotype. The BBD RDCRC is composed of 8 primary clinical sites (Houston, Los Angeles, Portland, Chicago, Montreal, New York City, Baltimore, Washington DC), 2 core sites (Seattle and Tampa), one training & advocacy site (Osteogenesis Imperfecta Foundation), and an Administrative unit (Houston). We propose two clinical projects. Project 1 is a Longitudial study of OI focused on correlating genotype to phenotype, natural history of vertebral fractures in OI type I, scoliosis in severe OI, pregnancy i OI, and craniofacial/dental features in severe Ol. Project 2 is a Phase I trial of an anti-TGFb therapy Fresolimumab in severe OI in the context of a dose ranging study followed by an extension repeat dosing study. There will be two Pilot Projects. The first focuses on the development of mass spectrometric analysis of urinary collagen cross-link patterns as a tool for distinguishing different mechanistic causes of Ol and for correlating with disease severity. The second focuses on validating aspects of the PROMIS tool for adults with OI. An important partner will be the Osteogenesis Imperfecta Foundation (OIF) and the Training and Advocacy activities will be coordianted by the OIF. They include establishment of a new fellowship for clinical research training, a clinical bone research training workshop, and development of a "tool box" of web-based training for primary healthcare providers to extend the knowledge gained by these studies to patients. Finally, the administration of the BBD RDCRC will be based in Houston at the Baylor College of Medicine. The BBD RDCRC will be leveraged by resources from the OIF who will directly support two of the clinical sites and a pilot project on PROMIS, the Shriners Hospital system, and institutional commitments from Baylor College of Medicine. The BBD RDCRC is built on established cohorts of the OIF Linked Longitudinal Clinical Research Centers and established expertise in pediatric and adult interventional studies that demonstrates a track record of success in patient advocacy, recruitment, and retention for clinical research studies.

描述（由申请人提供）： 这是一项申请，旨在建立一个脆性骨骼疾病罕见病临床研究联盟（BBD RDCRC），专注于研究13种以上不导致成骨不全（OI）表型的遗传疾病。BBD RDCRC由8个主要临床研究中心（休斯顿、洛杉矶、波特兰、芝加哥、蒙特利尔、纽约市、巴尔的摩、华盛顿DC）、2个核心研究中心（西雅图和坦帕）、1个培训和宣传研究中心（成骨缺陷基金会）和1个行政单位（休斯顿）组成。我们提出了两个临床项目。项目1是一项OI纵向研究，重点是将基因型与表型、I型OI椎体骨折自然史、重度OI脊柱侧凸、妊娠OI和重度OI颅面/牙齿特征相关联。项目2是在剂量范围研究和随后的扩展重复给药研究的背景下在重度OI中进行的抗TGF β治疗Fresolimumab的I期试验。将有两个试点项目。第一个重点是尿胶原交联模式的质谱分析的发展，作为区分OI的不同机制原因和与疾病严重程度相关的工具。第二个重点是验证PROMIS工具的成人OI方面。一个重要的合作伙伴将是成骨缺陷基金会，培训和宣传活动将由该基金会协调。这些措施包括设立一个新的临床研究培训奖学金、一个临床骨骼研究培训工作坊，以及为基层医疗服务提供者开发一个网上培训“工具箱”，以便将这些研究所获得的知识推广到病人身上。最后，BBD RDCRC的管理将设在休斯顿的贝勒医学院。BBD RDCRC将利用OIF的资源，OIF将直接支持两个临床研究中心和PROMIS试点项目， Shriners医院系统和贝勒医学院的机构承诺。BBD RDCRC建立在OIF相关纵向临床研究中心的既定队列以及儿科和成人干预性研究的既定专业知识基础上，这些研究证明了临床研究在患者宣传、招募和保留方面的成功记录。