Pilot project

Boston Children'S Hospital, Boston MA

Investigators

Linked publications & trials

Abstract

Project Summary/Abstract Within the Developmental Synaptopathies Consortium (DSC), we have chosen approaches and tools that can be implemented rigorously at the DSC sites in order to leverage the large number of patients with neuropsychiatric manifestations in TSC, PHTS, and PMS and enable cross-syndromic comparisons between these disorders. In DSC-III, we will add SYNGAP1-ID to this group. We will complement our prior approaches to also initiate pilot studies that can be performed by investigators in smaller patient cohorts and that have the ability to inform future studies. Since its inception in 2014, the DSC has built a robust and effective infrastructure across the involved institutions to collect standardized neuropsychological assessments documenting the natural history of these rare genetic conditions. An innovative component of this Consortium has been driven by pilot projects, in several cases motivated and funded by the patient advocacy groups. Highlights of the pilot projects supported by the DSC to date include: a Phase I/II clinical trial investigating the safety and efficacy of an mTOR inhibitor (everolimus) in individuals with PHTS (clinicaltrials.gov NCT02991807); mapping the phenotype in adults with PMS (NCT03426059); a pilot study exploring novel electrophysiological biomarkers of PMS; and two pilot studies initiated by junior investigators to address gaps in our understanding of the clinical presentation of and access to care in TSC and PHTS, which occurred during the first grant cycle. An additional three pilot projects that were disease-specific to TSC, PHTS, and PMS took place and are ongoing as part of the second grant cycle. For evaluation of all pilot projects and data access requests, we developed a formal and standardized application process. In this funding period, we propose to expand on this track record of success by utilizing the Pilot/Feasibility Core (PFC), which will be made up of the co-leadership of Drs. Buxbaum and Bebin, the Administrative Coordinator, External Advisory Committee members, and Patient Advocacy Group representatives. The PFC will be responsible for determining the research priorities and focus areas; mentoring potential pilot investigators; performing a thorough review of the proposals; overseeing and supporting pilot projects; and monitoring their progress. Review of pilot projects by the PFC will follow NIH procedures to approve new protocols. Additionally, the PFC will ensure all studies adhere to relevant regulations and policies regarding human subject research, obtain prior IRB approval, and submit inclusion enrollment information and regular progress reports. Working together with the patient advocacy groups, we will make every effort to disseminate the announcement of the pilot project RFA broadly to investigators both within the DSC, as well as those outside the DSC institutions. The PFC will work with the Administrative Core to disseminate the results of pilot studies to investigator and patient communities.