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Sex Differences in Statural Growth Impairment in Pediatric Crohn's Disease: Part 2

Award Number: R01HD111638
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/11/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Sex Differences in Statural Growth Impairment in Pediatric Crohn's Disease: Part 2 - Project Summary/Abstract Growth impairment is a common complication of pediatric Crohn’s disease. Normalization of growth is a marker of disease control and successful Crohn’s disease therapy. Treatment strategies for improving growth impairment and final adult height are currently suboptimal. The impact of Crohn’s disease on growth is potentially mediated by many factors, including inflammation, genetics, microbiome, nutrition, and medications. The continued presence of growth impairment primarily reflects continued suboptimal treatment of the underlying inflammation characteristic of Crohn’s disease. We hypothesize that the inflammation characteristic of Crohn’s disease has greater negative effects on endocrine growth regulators (IGF-1 levels, sex hormone levels, and gonadotropin levels) in males and that these greater negative inflammatory effects help to explain the increased susceptibility to growth impairment in males. This hypothesis is based on our analyses of data collected from our completed prospective multicenter longitudinal study of sex differences in growth impairment (Growth Study Part 1). Our Part 1 data show that as bone age progresses, standardized height gain is lower in males. Our Part 1 findings suggest inflammation exerts a greater negative effect on hormone levels and growth in males, and indicate that sex-specific molecular pathways lead to growth impairment in children with Crohn’s disease. The primary pathway to growth impairment appears be the growth hormone/IGF-1 axis in males and the hypothalamic/pituitary/gonadal axis in females. Developing a sex-specific risk-based treatment approach for children with Crohn’s disease is essential. However, the specific molecular mechanisms causing sex differences in growth impairment remain poorly characterized. Here, we propose to expand and continue to follow our cohort to harvest information on the proteome (Aim 1) and genome (Aim 2) to provide new insights into growth impairment. These data will enhance our ability to determine the underlying mechanisms of sex differences in growth impairment (Aims 1 and 2) and develop robust sex-specific predictive models to identify high-risk patients (Aim 3). Part 2 of the Growth Study will generate essential data that will enable us to develop a highly needed sex-specific risk- based pediatric Crohn’s disease treatment approach, which will represent a major paradigm shift in clinical practice. Institution of appropriate personalized sex-specific risk-based medical therapies targeting the underlying inflammation (since improved growth results from improved disease control) is essential since only a very narrow therapeutic interval is available to intervene to improve growth before growth plates close.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $667,497 )
2025	2025	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Child Health and Human Development Extramural Research	000	3	6/13/2025	NON-COMPETING CONTINUATION	$667,497
														Subtotal = $667,497

Issue Date FY: 2024 ( Subtotal = $674,101 )
2024	2024	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Child Health and Human Development Extramural Research	000	2	7/19/2024	NON-COMPETING CONTINUATION	$674,101
														Subtotal = $674,101

Issue Date FY: 2023 ( Subtotal = $732,615 )
2023	2023	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Child Health and Human Development Extramural Research	000	1	9/11/2023	NEW	$732,615
														Subtotal = $732,615

Grand Total All Awards = $2,074,213

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Sex Differences in Statural Growth Impairment in Pediatric Crohn's Disease: Part 2

Award Number: R01HD111638

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/11/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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