NIH SIREN Neurologic Clinical Trials (UG3/UH3 - Clinical Trial Required) PAR-25-049

The National Institutes of Health (NIH), through its National Institute of Neurological Disorders and Stroke (NINDS), is offering funding under the NIH SIREN Neurologic Clinical Trials initiative (PAR-25-049), which supports multi-center clinical trials focused on neurological emergencies. Successful applicants will collaborate within the NIH Strategies to Innovate Emergency Care Clinical Trials Network (SIREN), leveraging its infrastructure, which includes a Clinical Coordinating Center (CCC), a Data Coordinating Center (DCC), and a network of clinical sites organized under a Hub and Spoke model. The CCC will assist with trial implementation, while the DCC provides statistical and data management support. Applicants are not required to be existing SIREN members to apply. The objective of this opportunity is to encourage trials in neurological emergencies such as status epilepticus, traumatic brain injury, spinal cord injury, and headache. Stroke-related trials should instead utilize the NINDS-supported StrokeNet. Applications must propose hypothesis-driven, simple, and pragmatic clinical trials. These trials should feature straightforward patient eligibility criteria, integrate well with standard care, and involve limited data collection. The scope includes interventions such as novel devices or medications, comparisons of existing treatments, and large pragmatic trials, but excludes registries or descriptive observational studies. Early exploratory studies (e.g., dose-ranging) are not eligible. Applicants must integrate SIREN infrastructure into their trial design, including coordination through the CCC and data management through the DCC. They are strongly encouraged to engage with NINDS staff, SIREN leadership, and both coordinating centers early in the process to develop robust research and budget plans. Trials must adhere to NIH requirements for data sharing and must obtain necessary regulatory approvals (IND/IDE) before submission. All applicants are required to use SIREN’s master clinical trial agreements and central IRB. Eligible applicants include a wide range of U.S. and non-U.S. entities, such as higher education institutions, nonprofits, for-profit organizations, governments, independent school districts, tribal organizations, and foreign organizations. Each application must follow detailed instructions provided in the NIH Application Guide and this Notice of Funding Opportunity (NOFO), including requirements for a letter of intent, study milestones, and data and safety monitoring plans. The funding opportunity has multiple application due dates through March 2026. Key deadlines include a Letter of Intent due 30 days prior to the application deadline and specific submission dates in February, June, and October each year. Applications undergo NIH peer review and must meet milestones to transition from the UG3 (initial phase) to the UH3 (full clinical trial phase). The total project period is typically up to five years, with specific funding amounts based on project needs. Contact information includes Jeremy Brown, MD (jeremy.brown@nih.gov and NINDS_SIREN@ninds.nih.gov) for scientific/research inquiries and the NINDS Grants Management Officer (ChiefGrantsManagementOfficer@ninds.nih.gov) for financial/grants management questions.