Brittle Bone Disorders Consortium of the Rare Disease Clinical Research Network

Baylor College Of Medicine, Houston TX

Investigators

Linked publications, trials & patents

Abstract

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 11-16, the final and third cycle. The BBDC is focused on rare bone diseases (RBD) that are caused by defects in osteoblast differentiation and/or function which leads to qualitative and/or quantitative defects of bone, altered biomaterial properties, and/or downstream cellular changes in bone cells. These are represented by the different types of Osteogenesis Imperfecta (OI) which now include association with over 23 genes. While OI is often used interchangeably with BBD and the phenotypic spectrum is rapidly expanding, they have in common early bone fragility and fracture. Moreover, there is a significant unmet need to understand the natural history of these phenotypes stratified by their molecular genetic etiologies. How 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 1-10 of the BBDC, we met or exceeded accrual targets in 6 out of 10 protocols with active recruitment in the remaining 4. We have published close to 50 manuscripts describing our primary cross sectional data, patient engagement experience, and review of treatment approaches. Importantly, unmet needs identified by the largest international survey of OI adults to date identify pain as the major issue from patient-lived experiences. At the same time, our data sharing and industry collaborations highlighted the need for better, quantitative surrogate endpoints to overcome disease heterogeneity in clinical interventional trials. Hence, in this final cycle, Project 1 will be completion of our longitudinal study with focus on completing at least 6 years of follow up for the 1000 enrolled subjects, generation of whole genome sequences (WGS) and return of pathogenic results to subjects and CLINVAR to accelerate diagnoses, and central reading of over 4000 radiographs to address scoliosis and vertebral progression; Project 2 will be a mindful self-compassion (MSC) pain interference clinical study, whose bio-psychological intervention is based on pilot engagement and trial generated in the current cycle; Project 3 will study the longitudinal (re)modeling quantified by high-resolution peripheral quantitative and cone beam computed tomography (HR-pQCT and CBCT) as phenotypic endpoints for disease progression. Our Administrative Core (AC) will facilitate collaboration, implementation of protocols and processes, and oversight of protocols. Our Pilot and Feasibility Core (PFC) will build on our successes to solicit opportunities from both inside and outside the consortium to identify unmet needs for pilot studies. Our Career Enhancement Core (CEC) will build on our successes in patient, trainee, and provider engagement in comprehensive fashion utilizing formal didactic virtual programming, salary support for training, convening RBD experts in scientific meetings, and leveraging broad sharing platforms for content delivery. In so doing, we hope to provide a foundation for future sustained investment in RBD research.