NIH funding opportunities (3) - Research to Advance the Understanding and Management of the Multiple Organ Dysfunction Syndrome in Children (R01, R03, R21)

The following description is taken from the R01 version of this FOA.

Multiple organ dysfunction syndrome (MODS) is a clinical condition commonly encountered in the pediatric intensive care unit that is associated with significant morbidity and mortality. It is characterized by the failure or dysfunction of a consistent group of body organs or organ systems. It is triggered by a wide range of disease processes and clinical insults, most notably sepsis and trauma, and is frequently associated with uncontrolled inflammation. Although quite varied, some published reports suggest an incidence as high as 57% among patients admitted to the pediatric intensive care unit (PICU). Large scale data suggest that nearly 20% of children will have MODS on their first day of PICU admission; these children have nearly a 10-fold greater chance of dying. Moreover, mortality from MODS increases with each additional failing organ. Data suggest that for every additional organ dysfunction, the risk of mortality doubles. Despite the high prevalence and these unfavorable outcomes, this clinical entity remains poorly understood. First described approximately 40 years ago, it is still can only be described as a “syndrome”, a constellation of symptoms, rather than as a specific pathologic entity with a distinguishable cause. To most effectively advance the field of pediatric critical care, much more needs to be learned about this life-threatening syndrome. The NICHD recently sponsored a Workshop of multidisciplinary experts in the field of Pediatric MODS to describe the state of the science and to identify key areas for research. Through those informative sessions, it was affirmed that the study of MODS in children must be a high priority, and that advancements in this field offered the potential and promise of transforming outcomes of critically ill children. Five broad areas of study were identified for MODS including: 1) epidemiology and outcomes; 2) detection and monitoring of MODS; 3) pathophysiology; 4) specific triggering etiologies; and 5) promising therapies.

Scope

The scope of this funding opportunity is to address the many specific areas where knowledge gaps exist and research needs remain. To address these diverse issues most effectively, a wide range of science must be conducted ranging from basic science molecular and genomic studies up to large scale, longitudinal epidemiology projects and clinical trials. Consequently, there is a need for large scale research project grants to support such study. Applications for this FOA may address (but are not limited to) one or more of the following five priority areas:

Epidemiology and Outcomes

Studies directed at developing and validating new definitions of the syndrome that are evidence-based and expanded to include contemporary data such as biomarker levels.
Studies designed to secure large scale epidemiology data needed to most completely understand the precipitants of the syndrome, assess the magnitude of the problem and establish the long-term outcomes beyond simply hospital survival.

Detection and Monitoring of MODS

Studies aimed at the re-assessment of clinical criteria for diagnosing and monitoring the progression of MODS given advancements in monitoring capabilities over time.
Studies designed to identify associations between biomarker levels and MODS; identified relationships must be further validated in prospective, multicenter study, and performed in a manner to be clinically relevant.
Studies attempting to identify unique endotypes and phenotypes that may exist among those given the global diagnosis of MODS.
Studies that test novel techniques and technologies used in the diagnosis and monitoring of MODS which may include, but are not limited to, the following:
Mechanistic, mathematical modeling
Redox monitoring
Assessment of heart and respiratory rate variation
Continuous, real-time assessment of biomarker levels
Non-invasive monitoring of biomarkers through sweat and other mechanisms

Pathophysiology

Studies directed at elucidating the complex, inter-related pathophysiologic processes associated with this condition.
Studies aimed at identifying mechanisms common to all MODS patients as well as those developed to characterize pathophysiologic features unique to specific phenotypes.
Basic science studies designed to identify the most rudimentary cause of the syndrome at a molecular, cellular and genomic level that can then be advanced into translational and clinical projects.
Studies focused on specific pathophysiologic processes that include, but are not limited to, any of the following:
The role of damage-associated molecular pattern molecules (DAMPs) and pathogen-associated molecular pattern molecules (PAMPs)
Hyperinflammatory syndromes
Thrombocytopenia-associated multiple organ failure
Mitochondrial dysfunction
Immunoparalysis
Endothelial and epithelial injury
Alterations in redox potentials
Gastrointestinal perturbations
Alterations in the microbiome

Specific Triggering Etiologies

Studies focused on the assessment of MODS within specific disease categories (e.g. MODS among children with sepsis, cancer, acute respiratory distress syndrome, congenital heart disease, inborn errors of metabolism, etc.).
Studies designed to compare MODS across different disease categories identifying key similarities and differences in terms of pathophysiology, epidemiology, and outcomes.
Studies directed at the assessment and occurrence of MODS in children who have experienced external injury such as trauma and burn victims.
Studies aimed at minimizing the occurrence of MODS associated with therapeutic interventions such as blood transfusions, medications, and organ and stem cell transplantation.

Promising Therapies

Large scale, multicenter, prospective clinical studies to assess the true value of therapies found to be effective in case series and small, uncontrolled trials.
Comparative effectiveness studies designed to identify the most effective therapies across centers including optimal supportive care.
Studies designed to assess and identify differences in responsiveness to therapies among all pediatric MODS patients.

Deadlines: standard dates apply

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Filed Under: Funding Opportunities

NIH funding opportunities (3) – Research to Advance the Understanding and Management of the Multiple Organ Dysfunction Syndrome in Children (R01, R03, R21)