The National Heart, Lung, and Blood Institute (NHLBI) seeks applications for Phase I clinical trials aimed at advancing diagnostic and therapeutic interventions for heart, lung, blood, and sleep (HLBS) disorders in adults and children. This funding opportunity focuses on investigator-initiated trials that assess safety, feasibility, and pharmacokinetics while addressing unmet medical needs and resource gaps. Single or multi-site trials may be proposed, and applicants must be prepared to commence the trial within the first quarter of the project period. This opportunity is reissued under PAR-25-025 and uses the R33 mechanism.

The program emphasizes the importance of milestone-driven research to ensure timely progress and budget adherence. Secondary aims may include dose optimization, safety evaluations, and development of clinical outcome measures for subsequent trials. NHLBI encourages studies that can rapidly transition to later phases of clinical evaluation. Applications requiring preclinical or trial-readiness activities should consider the companion announcement PAR-25-026.

Awards will be contingent on the quality of applications and availability of funds, with budgets capped at $1,515,000 annually in direct costs for a maximum project period of three years. Eligible applicants include domestic and foreign institutions, government entities, nonprofit and for-profit organizations, and higher education institutions, including minority-serving institutions. Applicants must be registered in SAM.gov, eRA Commons, and Grants.gov prior to submission. Investigators must also meet NIH clinical trial requirements and guidelines.

Applications must include a comprehensive research strategy, detailing significance, innovation, and a robust approach, as well as an explicit milestone plan to monitor progress. Applicants must also outline data management, recruitment, and retention strategies while addressing protections for human subjects and compliance with NIH policies. Required attachments include project management and clinical trial research experience documents.

Applications are subject to NIH peer review based on significance, rigor, feasibility, and the investigators' expertise and resources. Proposals must align with NHLBI’s mission and strategic priorities, with diversity and inclusion being a central focus. Key dates for submission are February 3, June 4, and October 2 annually through January 8, 2027. Submissions are accepted through ASSIST or Grants.gov Workspace.

Award recipients are responsible for compliance with NIH policies, including mandatory reporting, data sharing, and registration of clinical trials on ClinicalTrials.gov. Further inquiries regarding scientific and application-specific questions can be directed to NHLBI contacts listed in the announcement.