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ARPA-H: Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) Innovative Solutions Opening (ISO)

National Institutes of Health

The Advanced Research Projects Agency for Health (ARPA-H) is posting this Innovative Solutions Opening (ISO) solicitation in support of the Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) Program. ARPA-H anticipates that multiple Other Transaction (OT) Agreements will result from this announcement.

The CIRCLE program seeks to create a critical illness Control Point Validation Engine that leads to improvements in intensive care unit (ICU) health outcomes, coupled to reduced stay time and associated costs, by assessing, predicting, and treating immuno-inflammatory dysregulation before it causes organ failure. Critical illness is defined as multiple organ dysfunction requiring specialized medical treatment in an ICU, characterized by acute inflammation and immune dysregulation that propagates rapidly across most tissues, organs, and biofluids and severely impacts quality of life following hospital discharge. Critical illness may be initiated by physical trauma, infectious disease (sepsis), chronic disease (e.g., inflammatory bowel disease, liver cirrhosis, heart disease), stroke, or cancer. Current critical care paradigms are focused predominantly on organ support, with few avenues for the treatment of dysregulated immunoinflammation. To achieve these aims, the CIRCLE program seeks to obtain targeted near real-time patient data: tissue-specific and system (patient) assessments of critical illness immuno-inflammation biomarkers. These data will be used to define novel control points through validated computational digital twin models of critical illness that will direct personalized immunotherapy. This transformative program will expand our understanding, diagnosis, prognosis, and treatment of critical illness driven by diverse causes, ultimately also impacting chronic disease that is induced or exacerbated by critical illness. Importantly, CIRCLE will involve early integration of clinical translation efforts to accelerate the transition of these innovations to intensivists and their critically ill patients.

Each proposal responsive to this ISO may be of one of two types: they must either address all three TAs, “Type A”, or address a single AP component, “Type B”. CIRCLE is seeking a diversity of approaches for each TA, and therefore individuals and corporate units may not contribute to more than one Type A proposal. Additionally, to avoid conflicts of interest between TA performers and AP performers, no organization, whether acting as a primary or sub-performer, may participate in both a Type A and a Type B proposal. Interested applicants from within Duke should contact fundopps@duke.edu as early as possible as an application from Duke is being developed.

Proposal submission: Thursday, May 28, 2026, 1:00 PM

Specialties

Interdisciplinary

Medical - Basic Science

Medical - Translational

Medical

Medical - Clinical Science

Eligibility Requirements

Sponsor Details

Sponsor Institute/Organizations: National Institutes of Health

Sponsor Type: Government/Federal

Address: National Institutes of Health; 31 Center Drive; MSC 2220; Bethesda; MD 20892-2220; USA

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