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.
.
项目摘要/摘要
小儿克罗恩病(CD)的治疗目标已从临床改善或缓解转移到
磁共振肠肠镜检查和透壁愈合(TH)内窥镜愈合(EH)通过磁共振摄影
(MRE)。实现完全愈合(CH,EH和TH)的患者的住院或手术较少。我们
假设特定的预处理临床,放射学,转录组,基因组和微生物因子沿
随着靶向抗TNF生物学暴露的达到,将与主要终点,CH和
抗TNF启动52周后,主要的次要终点是EH和Th。我们将在
550个新诊断为抗TNF药物治疗的小儿发作的CD受试者的前瞻性队列研究
在诊断为治疗药物监测(TDM)的6个月内。
目标1。评估推定的关联并探索CH和基线之间的新型关联
临床和放射学严重程度的度量。我们假设治疗前的营养状况,
抗菌血清学和MRE发现将与1年级有关。正式的假设检验将是
使用适当控制的I型错误概率进行的,以确认一组预先的预测能力
使用逻辑回归模型基于1年的结果进行指定的基线测量。
AIM 2。评估推定的关联并探索抗TNF药物水平之间的新型关联,CH,
以及宿主和微生物基因组和转录组因子。我们假设该预处理基因
表达特征和微生物因子将与早期抗TNF药物水平和1年级有关。
我们将表征宿主基因型,基线粘膜和纵向粪便微生物分类学谱,以及
基线回肠和结肠宿主转录组。那些被确定为显着关联的变量将是
在AIM 3中确定的最终预测模型的候选人。
AIM 3。使用K折的交叉验证程序来确定1年级的最佳预测模型。
我们假设包括宿主基因特征和微生物在内的模型将改善CH的预测
仅仅基于临床和成像因子。该模型将包括临床和成像预测指标
从AIM 1和宿主和微生物特征中发现,在AIM 2中可以解释。
影响。拟议的Inception队列研究Cameo将为研究因素提供一个强大的平台
在小儿CD中的康复贡献,然后可以将其转化为实践,并指导未来的疗法
靶向宿主免疫反应和微生物群,不太可能实现愈合。
。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
LEE ARMISTEAD DENSON其他文献
LEE ARMISTEAD DENSON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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
预测标准化小儿结肠炎治疗的反应:PROTECT 研究
- 批准号:
8458111 - 财政年份:2012
- 资助金额:
$ 280万 - 项目类别:
相似国自然基金
机器学习辅助研究氮气在金属硫化物团簇上的活化与转化
- 批准号:22303096
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
机器学习辅助研究轻质合金表面涂层耐蚀耐磨及其功能化弹热性
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
代谢组学辅助研究纳米石墨烯协同黄麻修复农田土壤镉污染的行为及修复机制
- 批准号:52200207
- 批准年份:2022
- 资助金额:30.00 万元
- 项目类别:青年科学基金项目
机器学习辅助研究轻质合金表面涂层耐蚀耐磨及其功能化弹热性
- 批准号:52205189
- 批准年份:2022
- 资助金额:30.00 万元
- 项目类别:青年科学基金项目
代谢组学辅助研究纳米石墨烯协同黄麻修复农田土壤镉污染的行为及修复机制
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Anti-CCP Antibodies, TNF-Antagonists, and Cardiac Function in Rheumatoid Arthriti
类风湿性关节炎中的抗 CCP 抗体、TNF 拮抗剂和心脏功能
- 批准号:
8854029 - 财政年份:2013
- 资助金额:
$ 280万 - 项目类别:
Anti-CCP Antibodies, TNF-Antagonists, and Cardiac Function in Rheumatoid Arthriti
类风湿性关节炎中的抗 CCP 抗体、TNF 拮抗剂和心脏功能
- 批准号:
8677689 - 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:
Anti-CCP Antibodies, TNF-Antagonists, and Cardiac Function in Rheumatoid Arthriti
类风湿性关节炎中的抗 CCP 抗体、TNF 拮抗剂和心脏功能
- 批准号:
8514779 - 财政年份:2013
- 资助金额:
$ 280万 - 项目类别: