Clinical, Imaging, and Endoscopic Outcomes of Children Newly Diagnosed with Crohn's Disease
新诊断克罗恩病儿童的临床、影像学和内窥镜结果
基本信息
- 批准号:10560015
- 负责人:
- 金额:$ 280万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:AlgorithmsAncillary StudyAnti-Tumor Necrosis Factor TherapyBiologicalBiological FactorsBudgetsCharacteristicsChildChildhoodClinicalClinical TreatmentClinical/RadiologicCohort StudiesColonColonoscopyCrohn&aposs diseaseDataData Management ResourcesData SetDevelopmentDiagnosisDiseaseDisease remissionDoseDrug ExposureDrug MonitoringErythrocyte Sedimentation RateExhibitsFibroblastsFutureGene ExpressionGene Expression ProfileGenetic TranscriptionGenomicsGenotypeGoalsHealth ExpendituresHospitalizationImageImmune responseInflammatoryInstitutional Review BoardsIntestinesLogistic RegressionsMacrophageMagnetic ResonanceManualsMeasuresMicrobeMicrobial TaxonomyModelingMucous MembraneMultiomic DataNeoadjuvant TherapyNewly DiagnosedNutritional statusOperative Surgical ProceduresOutcomePathogenesisPatientsPediatric Crohn&aposs diseasePharmaceutical PreparationsPredictive FactorProbabilityProceduresProcessProspective, cohort studyProtocols documentationQuality of lifeRadiology SpecialtyReadingRefractoryRegimenReportingRiskSerologyServicesSeveritiesSpecific qualifier valueTNF geneTestingTherapeuticTranslatingValidationantimicrobialbiobankclinical practiceclinical remissionclinical research siteexperiencegenetic signaturegenotyped patientshealinghospitalization ratesimage archival systemimprovedinfliximabinsightmicrobialmicrobial communitymicrobial genomicsmicrobiotanoveloperationpredictive modelingprimary endpointresponsesecondary endpointseropositivetargeted treatmenttranscriptometranscriptomics
项目摘要
PROJECT SUMMARY/ABSTRACT
Therapeutic goals in pediatric Crohn's Disease (CD) have shifted from clinical improvement or remission to
endoscopic healing (EH) by ileocolonoscopy and transmural healing (TH) by magnetic resonance enterography
(MRE). Patients achieving complete healing (CH, EH and TH) experience fewer hospitalizations or surgery. We
hypothesize that specific pre-treatment clinical, radiologic, transcriptomic, genomic, and microbial factors along
with attainment of targeted anti-TNF biologic exposure will be associated with the primary endpoint, CH, and the
major secondary endpoints, EH and TH, 52 weeks after anti-TNF start. We will test this hypothesis in a
prospective cohort study of 550 newly diagnosed pediatric-onset CD subjects treated with anti-TNF medication
within 6 months of diagnosis guided by therapeutic drug monitoring (TDM).
Aim 1. Evaluate putative associations and explore novel associations between CH and baseline
measures of clinical and radiologic severity. We hypothesize that pre-treatment nutritional status,
antimicrobial serologies, and MRE findings will be associated with year 1 CH. Formal hypothesis tests will be
carried out with appropriately controlled Type I error probabilities to confirm the predictive power of a set of pre-
specified baseline measures using a logistic regression model based on the year 1 CH outcome.
Aim 2. Evaluate putative associations and explore novel associations between anti-TNF drug levels, CH,
and host and microbial genomic and transcriptomic factors. We hypothesize that pre-treatment gene
expression signatures and microbial factors will be associated with early anti-TNF drug levels and year 1 CH.
We will characterize the host genotype, baseline mucosal and longitudinal fecal microbial taxonomic profile, and
baseline ileal and colon host transcriptome. Those variables identified as significantly associated will be
candidates for the final prediction model determined in Aim 3.
Aim 3. Use a k-fold cross-validation procedure to determine the optimal predictive model of year 1 CH.
We hypothesize that a model which includes host gene signatures and microbes will improve prediction of CH
beyond one based on clinical and imaging factors alone. The model will include clinical and imaging predictors
from Aim 1 and host and microbial characteristics found to be potentially explanatory in Aim 2.
Impact. The proposed inception cohort study, CAMEO, will provide a robust platform to study factors that
contribute to healing in pediatric CD that can then be translated into practice, as well as guiding future therapies
targeting the host immune response and microbiota in patients unlikely to achieve healing.
.
项目总结/摘要
儿童克罗恩病(CD)的治疗目标已从临床改善或缓解转向
通过回结肠镜检查进行内镜下愈合(EH),通过磁共振小肠造影检查进行透壁愈合(TH
(MRE)。实现完全愈合的患者(CH、EH和TH)经历较少的住院或手术。我们
假设特定治疗前临床、放射学、转录组、基因组和微生物因素沿着
达到靶向抗TNF生物制剂暴露将与主要终点CH相关,
主要次要终点,EH和TH,抗TNF治疗开始后52周。我们将在一个
在550例接受抗TNF药物治疗的新诊断儿童发病CD受试者中开展的前瞻性队列研究
在治疗药物监测(TDM)指导下诊断的6个月内。
目标1。评估CH和基线之间的假定关联并探索新的关联
临床和放射学严重程度的测量。我们假设治疗前的营养状况,
抗菌血清学和MRE结果将与第1年CH相关。
进行了适当控制的I型错误概率,以确认一组预-
使用基于第1年CH结果的逻辑回归模型指定基线测量。
目标2.评价抗TNF药物水平、CH、
以及宿主和微生物基因组和转录因子。我们假设治疗前基因
表达特征和微生物因子将与早期抗TNF药物水平和1年CH相关。
我们将描述宿主基因型、基线粘膜和纵向粪便微生物分类特征,
基线回肠和结肠宿主转录组。被确定为显著相关的变量将是
目标3中确定的最终预测模型的候选者。
目标3。使用k折交叉验证程序确定第1年CH的最佳预测模型。
我们假设一个包括宿主基因签名和微生物的模型将改善CH的预测
而不仅仅是基于临床和成像因素。该模型将包括临床和成像预测因子
目标1和目标2中发现的宿主和微生物特征可能具有解释性。
冲击拟议的初始队列研究CAMEO将提供一个强大的平台来研究
有助于儿科CD的愈合,然后可以转化为实践,并指导未来的治疗
靶向不太可能实现愈合的患者的宿主免疫反应和微生物群。
.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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LEE ARMISTEAD DENSON其他文献
LEE ARMISTEAD DENSON的其他文献
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{{ truncateString('LEE ARMISTEAD DENSON', 18)}}的其他基金
Genetic Regulation of Tissue Fibrosis in Human Intestinal Organoids
人类肠道类器官组织纤维化的基因调控
- 批准号:
10428618 - 财政年份:2021
- 资助金额:
$ 280万 - 项目类别:
Clinical, imaging, and endoscopic outcomes of children newly diagnosed with Crohn's disease
新诊断克罗恩病儿童的临床、影像学和内镜结果
- 批准号:
10292286 - 财政年份:2021
- 资助金额:
$ 280万 - 项目类别:
Genetic Regulation of Tissue Fibrosis in Human Intestinal Organoids
人类肠道类器官组织纤维化的基因调控
- 批准号:
10191137 - 财政年份:2021
- 资助金额:
$ 280万 - 项目类别:
Dosing and Pilot Efficacy of 2'-Fucosyllactose in Inflammatory Bowel Disease
2-岩藻糖基乳糖治疗炎症性肠病的剂量和试验效果
- 批准号:
10394798 - 财政年份:2018
- 资助金额:
$ 280万 - 项目类别:
Dosing and Pilot Efficacy of 2'-Fucosyllactose in Inflammatory Bowel Disease
2-岩藻糖基乳糖治疗炎症性肠病的剂量和试验效果
- 批准号:
9883036 - 财政年份:2018
- 资助金额:
$ 280万 - 项目类别:
Causes and consequences of neutrophil dysfunction in early onset Crohn's disease
早发型克罗恩病中性粒细胞功能障碍的原因和后果
- 批准号:
8735941 - 财政年份:2013
- 资助金额:
$ 280万 - 项目类别:
Causes and consequences of neutrophil dysfunction in early onset Crohn's disease
早发型克罗恩病中性粒细胞功能障碍的原因和后果
- 批准号:
9116212 - 财政年份:2013
- 资助金额:
$ 280万 - 项目类别:
Causes and consequences of neutrophil dysfunction in early onset Crohn's disease
早发型克罗恩病中性粒细胞功能障碍的原因和后果
- 批准号:
9932706 - 财政年份:2013
- 资助金额:
$ 280万 - 项目类别:
Causes and consequences of neutrophil dysfunction in early onset Crohn's disease
早发型克罗恩病中性粒细胞功能障碍的原因和后果
- 批准号:
8632332 - 财政年份:2013
- 资助金额:
$ 280万 - 项目类别:
Predicting Response to Standardized Pediatric Colitis Therapy: PROTECT Study
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- 批准号:
8458111 - 财政年份:2012
- 资助金额:
$ 280万 - 项目类别:
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