The National Heart, Lung, and Blood Institute (NHLBI) is reissuing its funding opportunity to support Phase 1 clinical trials for diagnostic and therapeutic interventions for heart, lung, blood, and sleep (HLBS) disorders in adults and children. This funding opportunity, under the R33 mechanism, is intended for investigator-initiated single or multi-site clinical trials, including bridging studies that allow extrapolation of data from one population to another. The primary objective of the award is to evaluate the safety, feasibility, and pharmacokinetics of early-phase interventions, while also facilitating future Phase 2 trials. Applicants must be ready to initiate the proposed clinical trial within the first quarter of the project period, with regulatory approvals and supply chains in place at the time of the award.

Eligible applicants include higher education institutions, nonprofit organizations, small businesses, for-profit organizations, and local, state, and federal governments. U.S.-based entities are eligible, while foreign organizations may not apply; however, foreign components of U.S. institutions are permitted. Individual investigators with the necessary expertise in clinical trial coordination, management, and product development are invited to apply. Applications must demonstrate multidisciplinary teams with sufficient experience to execute the proposed trial successfully, including recruitment and implementation capabilities. The program strongly encourages early engagement with NHLBI staff to ensure alignment with program goals and priorities.

The maximum budget for an R33 award is one million five hundred fifteen thousand dollars in direct costs per year, with a total project period of up to three years. Applications must include clear milestones that are relevant, measurable, and time-bound, covering critical aspects of trial initiation, recruitment, data collection, and reporting. Milestones will be subject to NHLBI administrative review, and continued funding will depend on satisfactory progress. Performance metrics, such as enrollment goals and publication timelines, will be regularly monitored.

Proposals must address the study’s significance, innovation, and approach. The research strategy should include robust supporting data, a detailed experimental approach, and contingency plans for addressing potential risks. A comprehensive project management plan is required to ensure the trial’s timely and cost-efficient execution. For multi-site trials, the proposal must describe site capabilities, coordination plans, and enrollment strategies. Data management, quality control procedures, and statistical analyses must also be detailed. Proposals involving investigational new drugs or devices must include regulatory approval status and supporting documentation.

Applicants must comply with NIH’s requirements for human subjects research, including protections for participants, data and safety monitoring plans, and strategies to promote diversity in study populations. Special consideration will be given to the inclusion of women, minorities, and individuals across the lifespan. Applications must demonstrate how the proposed trial addresses an unmet need and advances the therapeutic or diagnostic intervention toward Phase 2 trials.

Applications are due on NIH standard submission dates, with the next deadlines being June fourth, two thousand twenty-four, October second, two thousand twenty-four, and February third, two thousand twenty-five. A letter of intent, though optional, is encouraged at least thirty days before the submission date. Applications must be submitted through Grants.gov, and applicants should allow time for error correction during the submission process. Awards will be contingent on scientific merit, program relevance, and the availability of funds. NHLBI staff will provide oversight through regular monitoring, and results must be reported to ClinicalTrials.gov.

Applicants are encouraged to contact NHLBI program staff early in the application process to ensure alignment with NHLBI’s mission and strategic priorities. The award will adhere to NIH policies, including data sharing requirements and post-award reporting obligations. For further information, prospective applicants may contact NHLBI program, peer review, and grants management staff listed in the announcement.