Brittle Bone Disorders Consortium of the Rare Disease Clinical Research Network

描述(由申请人提供)： 这是一项建立脆性骨骼疾病罕见疾病临床研究联盟(BBD RDCRC)的申请，该联盟专注于研究13种以上与成骨不全(OI)表型无关的遗传疾病。BBD RDCRC由8个初级临床站点(休斯顿、洛杉矶、波特兰、芝加哥、蒙特利尔、纽约市、巴尔的摩、华盛顿特区)、2个核心站点(西雅图和坦帕)、1个培训和宣传站点(成骨不完美基金会)和一个管理单位(休斯顿)组成。我们提出了两个临床项目。项目1是一项OI的纵向研究，重点关注OI的表型、OI I型脊柱骨折的自然病史、重度OI的脊柱侧弯、妊娠OI以及重度OL的头面部/牙齿特征之间的相关性。项目2是在剂量范围研究和扩大重复给药研究的背景下，抗TGFb治疗严重OI的Fsolimumab的I期试验。将有两个试点项目。第一个重点是发展尿胶原蛋白交联模式的质谱分析，作为区分OL不同发病机制以及与疾病严重程度相关的工具。第二个重点是验证成人OI PROMIS工具的各个方面。一个重要的合作伙伴将是成骨不完美基金会(OIF)，培训和宣传活动将由OIF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，以及为初级保健提供者开发一个基于网络的培训“工具箱”，以将这些研究获得的知识推广到患者身上。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将直接支持其中两个临床站点和PROIS上的一个试点项目，即 Shriners医院系统，以及贝勒医学院的机构承诺。BBD RDCRC建立在OIF链接的纵向临床研究中心的现有队列和儿科和成人干预研究方面的成熟专业知识的基础上，这些专业知识证明了临床研究研究在患者倡导、招募和保留方面的成功记录。

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.