Phase 1 study of oral epigallocatechin-3-gallate (EGCG) in IPF patients
IPF 患者口服表没食子儿茶素-3-没食子酸酯 (EGCG) 的 1 期研究
基本信息
- 批准号:10418169
- 负责人:
- 金额:$ 45.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-20 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAttenuatedBindingBiological MarkersBiologyBiopsyBloodChemistryClinicalClinical TrialsClinical Trials DesignCollagenCollagen Type IConsumptionDataDepositionDevelopmentDiagnosticDiseaseDoseDouble-Blind MethodEnrollmentEnsureEpigallocatechin GallateEpithelialExhibitsFDA approvedFamilyFibrillar CollagenFibroblastsFibrosisFutureGoalsGreen teaHealthHepaticHepatotoxicityHumanImageIn VitroInflammationInterstitial CollagenaseInterstitial Lung DiseasesLOX geneLOXL2 geneLaboratoriesLinkLungMeasuresModelingMolecular ProbesMonitorMusNational Heart, Lung, and Blood InstituteOperative Surgical ProceduresOralPathway interactionsPatientsPharmaceutical PreparationsPhasePhase II Clinical TrialsPhosphotransferasesPhysiologicalPilot ProjectsPirfenidonePlacebo ControlPlacebosPlantsPopulationPositron-Emission TomographyPrincipal InvestigatorProgressive DiseaseProtein-Lysine 6-OxidasePulmonary FibrosisRandomizedRenal functionReportingRoleSafetySerumSignal TransductionStructure of parenchyma of lungSurrogate MarkersTestingTimeTissuesToxic effectantifibrotic treatmentclinical research sitecohortcrosslinkdesigndrug developmenteffective therapyfollow-uphigh throughput screeningidiopathic pulmonary fibrosisin vivoindium-bleomycininhibitorinjuredinnovationinsightintervention costnanomolarnintedanibnovelpatient subsetsperiostinphase 1 studyphase 2 studyphase I trialphase II trialpre-clinicalpreclinical studyresponsesmall moleculetherapeutic targettreatment duration
项目摘要
PROJECT SUMMARY / ABSTRACT
The development of additional therapies for idiopathic pulmonary fibrosis is a pressing human health need. We
have identified epigallocatechin-3-gallate (EGCG), as potent (IC50 ~ 50-100 nM) blocker of TGFβ1 responses
ex vivo and new collagen deposition in vivo in the bleomycin model of pulmonary fibrosis. EGCG is a principal
component of green tea and has been utilized in multiple human studies. We have administered EGCG to
patients with pulmonary fibrosis for two weeks prior to undergoing lung biopsy and demonstrated highly
significant reversal of pro-fibrotic markers in lung tissue and decreases in blood biomarkers of TGFβ1
signaling. However, EGCG has not been given to patients with IPF in the setting of concurrent FDA-approved
IPF therapies and determination of the safety of EGCG in the setting of nintedanib or pirfenidone use is
essential given infrequent report of EGCG associated hepatotoxicity. The overarching goal of this proposal is
to define the safety and optimal dose of EGCG in IPF patients. We will use the R61/R33 mechanism to
conduct a robust randomized controlled Phase I trial to obtain additional critical safety and biomarker data
sufficient to empower a Phase II clinical trial to assess the efficacy of EGCG in IPF patients. A total of 5
cohorts of 10 IPF patients each at 6 clinical sites will be enrolled to receive EGCG. In Aim 1, we will determine
the safety of oral 400 mg and 600 mg EGCG given once daily to IPF patients for 12 weeks concurrent with
nintedanib or pirfenidone. We will also determine if 400 mg or 600 mg EGCG impacts nintedanib or pirfenidone
blood levels, and whether these antifibrotics alter the blood levels of EGCG. Clinical safety, especially
hepatotoxicity, will be monitored closely during the 12 week treatment duration and the 4 weeks of follow-up. In
Aim 2, we will measure the change in levels of prespecified serum biomarkers including COMP, Periostin, and
pro-MMP1 with EGCG treatment to determine if there is an in vivo signal for EGCG effect. Lastly, in Aim 3, we
will utilize the type I collagen-specific PET probe, 68Ga-CBP8 to determine the impact of EGCG in attenuating
lung accumulation. The results of Aim 2 and 3 will provide crucial information as to dose selection. This
proposal leverages the expertise of a multi-principal investigator team that are leaders in fibrosis biology and
clinical trial design, a low cost intervention, and an innovative molecular probe. The totality of this information
will provide key information needed to design a phase II with the ultimate goal of developing much needed IPF
therapies.
项目摘要/摘要
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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Harold A Chapman其他文献
Harold A Chapman的其他文献
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{{ truncateString('Harold A Chapman', 18)}}的其他基金
Phase 1 study of oral epigallocatechin-3-gallate (EGCG) in IPF patients
IPF 患者口服表没食子儿茶素-3-没食子酸酯 (EGCG) 的 1 期研究
- 批准号:
10702133 - 财政年份:2022
- 资助金额:
$ 45.38万 - 项目类别:
Program to promote lung regeneration and block fibrosis
促进肺再生和阻止纤维化的计划
- 批准号:
9893639 - 财政年份:2020
- 资助金额:
$ 45.38万 - 项目类别:
Program to promote lung regeneration and block fibrosis
促进肺再生和阻止纤维化的计划
- 批准号:
10570862 - 财政年份:2020
- 资助金额:
$ 45.38万 - 项目类别:
Epithelial stem/progenitor cells as repair agents in diffuse alveolar damage
上皮干/祖细胞作为弥漫性肺泡损伤的修复剂
- 批准号:
10181019 - 财政年份:2016
- 资助金额:
$ 45.38万 - 项目类别:
Epithelial stem/progenitor cells as repair agents in diffuse alveolar damage
上皮干/祖细胞作为弥漫性肺泡损伤的修复剂
- 批准号:
10418711 - 财政年份:2016
- 资助金额:
$ 45.38万 - 项目类别:
Epithelial stem/progenitor cells as repair agents in diffuse alveolar damage
上皮干/祖细胞作为弥漫性肺泡损伤的修复剂
- 批准号:
9355470 - 财政年份:2016
- 资助金额:
$ 45.38万 - 项目类别:
Epithelial Stem/Progenitor Cells in Repair of the Injured Lung
上皮干细胞/祖细胞修复受损肺
- 批准号:
9109038 - 财政年份:2015
- 资助金额:
$ 45.38万 - 项目类别:
Identification, Isolation, and Reprogramming Alveolar Epithelial Progenitor Cells
肺泡上皮祖细胞的鉴定、分离和重编程
- 批准号:
7676645 - 财政年份:2008
- 资助金额:
$ 45.38万 - 项目类别:
Urokinase Receptor Integrin Interactions in Lung Cancer
肺癌中尿激酶受体整合素相互作用
- 批准号:
7318124 - 财政年份:2007
- 资助金额:
$ 45.38万 - 项目类别:
Urokinase Receptor Integrin Interactions in Lung Cancer
肺癌中尿激酶受体整合素相互作用
- 批准号:
8079454 - 财政年份:2007
- 资助金额:
$ 45.38万 - 项目类别:
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