NICHD INCLUDE Project — Down Syndrome Research

INCLUDE Project — Clinical Trials Phased Awards

Funds phased clinical research programs for Down syndrome interventions through developmental and expansion awards.

The INCLUDE Project Clinical Trials Phased Awards (R61/R33) support rigorous clinical trial development addressing interventions for co-occurring conditions in people with Down syndrome across the lifespan. INCLUDE — Investigation of Co-occurring conditions across the Lifespan to Understand Down syndromE — is an NIH-wide initiative led by NICHD with co-participation from multiple NIH Institutes and Centers. The active NOFO is RFA-OD-27-005, which expires on June 16, 2028, with applications accepted on a rolling basis. The INCLUDE Project's broader investment context includes a $20 million Down Syndrome Cohort Development Program, reflecting sustained NIH commitment to this research area.

The R61/R33 is a two-phase mechanism: R61 funds clinical trial planning, protocol development, and feasibility assessment; R33 funds full trial implementation. Both phases are applied for within a single application — applicants do not submit R61 and R33 separately. This structure is designed for investigators who have promising intervention concepts that require systematic protocol development before a full trial can be executed. Eligible applicants include US-based universities, research organizations, non-profits, and small businesses; award ceilings and submission deadlines are specified in the NOFO.

Applications must address interventions relevant to Down syndrome or its co-occurring conditions — which span neurological, cardiovascular, immune, endocrine, and oncological domains given the systemic phenotype of trisomy 21. Because the R61/R33 mechanism gates R33 implementation on R61 milestones, reviewers will scrutinize the feasibility plan and go/no-go criteria carefully. Prospective applicants should consult with INCLUDE program officers across the participating NIH ICs before submission to align the intervention area and trial design with current portfolio gaps and strategic priorities.