Hyperbaric Oxygen Therapy for Ulcerative Colitis Patients Hospitalized for Moderate to Severe Flares: A Phase 3 Multi-Center, Randomized, Double-Blind, Sham-Controlled Trial
高压氧治疗因中度至重度发作而住院的溃疡性结肠炎患者:一项 3 期多中心、随机、双盲、假对照试验
基本信息
- 批准号:10561414
- 负责人:
- 金额:$ 243.96万
- 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:2023-03-15 至 2028-02-28
- 项目状态:未结题
- 来源:
- 关键词:AcuteAirAlgorithmsAtmospheric PressureBile AcidsBiological ProductsBreathingCaringCellsChronicClinicalClinical TrialsColectomyCollectionDiseaseDisease OutcomeDoseDouble-Blind MethodEpithelial CellsEpitheliumExclusionFecesFirmicutesFlareFrequenciesFunctional disorderFutureGlobal ChangeHIF1A geneHemorrhageHospital CostsHospitalizationHospitalsHumanHyperbaric OxygenHyperbaric OxygenationHypoxiaImmuneImmune systemInfectionInflammationInjuryIntestinal MucosaIntravenousMediatingMedicalMessenger RNAMetabolismMetagenomicsMicrobeMorbidity - disease rateMucin-2 Staining MethodMucous MembraneMucous body substanceOrphanOutcomeOxygenPathogenesisPathogenicityPathway interactionsPatientsPhasePopulationPostoperative PeriodPreventionProductionProgram DevelopmentRandomizedRectumResolutionRiskSTAT3 geneSalvage TherapySample SizeSideSteroid therapySteroidsTherapeuticTissuesTreatment EffectivenessTreatment EfficacyUlcerative ColitisUnited StatesWorkarmbile acid metabolismclinical remissioncohortcostdesigndigitaldrug developmenteffective therapyexperimental studygut microbiotahigh riskhigh risk populationhospital readmissionhost-microbe interactionsimprovedinflammatory markermetabolomicsmetatranscriptomicsmicrobialmicrobial compositionmicrobiomemortalityneutrophilnovelnovel therapeuticsparticipant enrollmentpatient populationphase II trialpressurepreventprimary outcomeprogramsprogression riskrectalresponsesmall moleculetissue injurytissue oxygenationtranscriptometranscriptomicstreatment response
项目摘要
PROJECT SUMMARY
Ulcerative colitis is one of the most expensive medical conditions in the United States, with a considerable
amount of these costs being incurred during hospitalizations for acute flares. A substantial proportion of
ulcerative colitis patients hospitalized for acute flares will fail to respond to intravenous steroids and
require second line therapies such as biologics and/or colectomy, which can be associated with significant
morbidity and mortality. Ulcerative colitis patients who are hospitalized or have recently been hospitalized
for acute flares are excluded from traditional phase 2 and 3 drug development trials because of how high
risk they are for progression to colectomy or re-admission. Novel, safe, and effective treatments are
needed to optimize outcomes in this high-risk orphan population. A hallmark of ulcerative colitis is chronic
intestinal mucosal hypoxia and inflammation, with an accompanying dysfunction in hypoxia response
pathways and preferential activation of pathogenic immune cells including neutrophils. Hyperbaric oxygen
therapy involves breathing 100% oxygen under increased atmospheric pressure to increase tissue
oxygenation. In a phase 2 trial program we demonstrated that this increased oxygenation of mucosal
tissue leads to improvements in disease activity in ulcerative colitis, reductions in inflammatory markers,
and prevention of progression to biologics or colectomy during hospitalizations for acute flares. In the
current proposal we aim to 1) confirm the impact of hyperbaric oxygen therapy on disease outcomes in
ulcerative colitis patients hospitalized for acute flares through a multi-center, double-blind, sham-
controlled, clinical trial. We further aim to explore the mechanisms through which hyperbaric oxygen
therapy improves disease activity by studying the hyperbaric oxygen specific effects on 2) neutrophils and
epithelial cells, and 3) the microbiome. Confirmation of treatment efficacy for hyperbaric oxygen therapy
would bring forward a novel therapy for a high-risk population of ulcerative colitis patients who are
traditionally excluded from traditional clinical trial programs, while also advancing our understanding of
disease pathogenesis and the interplay between hypoxia, the immune system, and the microbiome.
项目摘要
溃疡性结肠炎是美国最昂贵的医疗条件之一,
在急性发作住院期间发生的这些费用的金额。相当大比例的
因急性发作而住院的溃疡性结肠炎患者对静脉内类固醇没有反应,
需要二线治疗,如生物制剂和/或结肠切除术,这可能与显著的
发病率和死亡率。正在住院或最近住院的溃疡性结肠炎患者
传统的2期和3期药物开发试验排除了急性发作,因为
风险他们是进展到结肠切除术或再次入院。新颖、安全、有效的治疗方法,
需要优化这一高风险孤儿人群的结局。溃疡性结肠炎的一个标志是慢性的
肠粘膜缺氧和炎症,伴随缺氧反应功能障碍
途径和包括嗜中性粒细胞在内的致病性免疫细胞的优先激活。高压氧
治疗包括在增加的大气压力下呼吸100%的氧气,以增加组织
氧合在一项2期临床试验中,我们证明了这增加了粘膜的氧合,
组织导致溃疡性结肠炎中疾病活动的改善,炎性标志物的减少,
以及在急性发作住院期间防止进展为生物制剂或结肠切除术。在
目前的建议,我们的目标是1)确认高压氧治疗对疾病结果的影响,
溃疡性结肠炎急性发作住院患者通过一个多中心,双盲,假,
对照临床试验我们进一步的目标是探索高压氧通过
治疗通过研究高压氧对2)中性粒细胞的特异性作用来改善疾病活动性,
上皮细胞,和3)微生物组。高压氧治疗的疗效确认
将为溃疡性结肠炎患者的高危人群提出一种新的治疗方法,
传统上被排除在传统临床试验计划之外,同时也促进了我们对
疾病的发病机制以及缺氧、免疫系统和微生物组之间的相互作用。
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 }}
Lauren Balmert Bonner其他文献
Peer review of clinical and translational research manuscripts: Perspectives from statistical collaborators
临床和转化研究手稿的同行评审:统计合作者的观点
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:2.6
- 作者:
Phillip Schulte;Judith D. Goldberg;Robert A. Oster;W. Ambrosius;Lauren Balmert Bonner;Howard Cabral;Rickey E. Carter;Ye Chen;Manisha Desai;Dongmei Li;C. Lindsell;Gina‐Maria Pomann;E. Slade;Tor D. Tosteson;Fang Yu;Heidi Spratt - 通讯作者:
Heidi Spratt
Lauren Balmert Bonner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('Lauren Balmert Bonner', 18)}}的其他基金
Hyperbaric Oxygen Therapy for Ulcerative Colitis Patients Hospitalized for Moderate to Severe Flares: A Multi-Center, Randomized, Double-Blind, Sham Controlled Trial (HBOT-UC)
高压氧治疗因中度至重度发作而住院的溃疡性结肠炎患者:一项多中心、随机、双盲、假对照试验 (HBOT-UC)
- 批准号:
10592029 - 财政年份:2021
- 资助金额:
$ 243.96万 - 项目类别:
相似国自然基金
湍流和化学交互作用对H2-Air-H2O微混燃烧中NO生成的影响研究
- 批准号:51976048
- 批准年份:2019
- 资助金额:61.0 万元
- 项目类别:面上项目
相似海外基金
Development of algorithms to optimize urban forestry for climate change and air pollution mitigation
开发优化城市林业以应对气候变化和空气污染的算法
- 批准号:
469896-2014 - 财政年份:2014
- 资助金额:
$ 243.96万 - 项目类别:
Engage Grants Program
CAREER: Practical Algorithms for Next Generation Air Transportation Systems
职业:下一代航空运输系统的实用算法
- 批准号:
0745237 - 财政年份:2008
- 资助金额:
$ 243.96万 - 项目类别:
Standard Grant
EFRI-ARESCI: Theory and Algorithms for Autonomous Reconfigurability of the National Air Transportation System
EFRI-ARESCI:国家航空运输系统自主重构的理论和算法
- 批准号:
0735905 - 财政年份:2007
- 资助金额:
$ 243.96万 - 项目类别:
Standard Grant
Real-time energy management control algorithms for heating, ventilating and air conditioning systems
适用于供暖、通风和空调系统的实时能源管理控制算法
- 批准号:
36380-2002 - 财政年份:2006
- 资助金额:
$ 243.96万 - 项目类别:
Discovery Grants Program - Individual
Diagnostic algorithms for air brakes in trucks: Theory and experiments
卡车空气制动器的诊断算法:理论与实验
- 批准号:
0556343 - 财政年份:2006
- 资助金额:
$ 243.96万 - 项目类别:
Standard Grant
Real-time energy management control algorithms for heating, ventilating and air conditioning systems
适用于供暖、通风和空调系统的实时能源管理控制算法
- 批准号:
36380-2002 - 财政年份:2005
- 资助金额:
$ 243.96万 - 项目类别:
Discovery Grants Program - Individual
Real-time energy management control algorithms for heating, ventilating and air conditioning systems
适用于供暖、通风和空调系统的实时能源管理控制算法
- 批准号:
36380-2002 - 财政年份:2004
- 资助金额:
$ 243.96万 - 项目类别:
Discovery Grants Program - Individual
air cushion vehicle bag and finger skirt optimization using genetic algorithms
使用遗传算法优化气垫车包和指裙
- 批准号:
227747-2001 - 财政年份:2003
- 资助金额:
$ 243.96万 - 项目类别:
Discovery Grants Program - Individual
Real-time energy management control algorithms for heating, ventilating and air conditioning systems
适用于供暖、通风和空调系统的实时能源管理控制算法
- 批准号:
36380-2002 - 财政年份:2003
- 资助金额:
$ 243.96万 - 项目类别:
Discovery Grants Program - Individual
air cushion vehicle bag and finger skirt optimization using genetic algorithms
使用遗传算法优化气垫车包和指裙
- 批准号:
227747-2001 - 财政年份:2002
- 资助金额:
$ 243.96万 - 项目类别:
Discovery Grants Program - Individual