Hyperbaric Oxygen Therapy for Ulcerative Colitis Patients Hospitalized for Moderate to Severe Flares

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

• 批准号: 10295441
• 负责人: Parambir Singh Dulai
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-06 至 2022-02-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10295441
• 关键词: Acute; Air; Algorithms; Atmospheric Pressure; Biological; Breathing; Caring; Cells; Chronic; Clinical; Clinical Trials; Clinical Trials Database; Clinical Trials Design; Colectomy; Contracts; Controlled Clinical Trials; Cyclosporine; Cytoplasmic Granules; Data; Disease; Disease Outcome; Dose; Double-Blind Method; Enrollment; Epithelial; Exclusion; Feces; Flare; Frequencies; Functional disorder; Health Expenditures; Healthcare Systems; Hemorrhage; Hospital Costs; Hospitalization; Hospitals; Human; Hyperbaric Oxygen; Hyperbaric Oxygenation; Hypoxia; Hypoxia Inducible Factor; Immune; Immune response; Immune system; Infection; Inflammation; Intestinal Mucosa; Intravenous; Investigation; Mediating; Medical; Messenger RNA; Metabolism; Metagenomics; Morbidity - disease rate; Mucous Membrane; Orphan; Outcome; Oxygen; Participant; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Phase; Phase III Clinical Trials; Population; Postoperative Period; Prevention; Program Development; Proteins; Randomized; Resolution; Risk; STAT3 gene; Salvage Therapy; Sample Size; Side; Specificity; Steroid therapy; Steroids; T-Lymphocyte; Therapeutic; Tissues; Treatment Effectiveness; Treatment Efficacy; Ulcerative Colitis; United States; United States Food and Drug Administration; Work; arm; clinical remission; cohort; cost; digital; drug development; effective therapy; high risk; high risk population; hospital readmission; hospitalization rates; improved; inflammatory marker; infliximab; insight; metabolomics; metaproteomics; microbial; microbial composition; microbiome; mortality; multiple omics; neutrophil; novel; novel therapeutics; patient population; phase II trial; phase III trial; pressure; prevent; primary outcome; programs; rectal; response; tissue oxygenation; transcriptomics; treatment response

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, phase 3 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 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.

溃疡性结肠炎是美国最昂贵的医疗疾病之一，有相当大的 这些费用的数额是在因急性照明弹住院期间发生的。相当大比例的 溃疡性结肠炎患者因急性炎症而住院，对静脉注射类固醇和 需要生物制剂和/或结肠切除术等二线治疗，这可能与显著相关 发病率和死亡率。正住院或最近曾住院的溃疡性结肠炎患者 因为急性耀斑被排除在传统的2期和3期药物开发试验之外，因为 它们有可能进展为结肠切除术或再次入院。新颖、安全、有效的治疗方法是 需要优化这一高危孤儿群体的结果。溃疡性结肠炎的一个特征是慢性 肠粘膜缺氧和炎症，伴随低氧反应功能障碍 包括中性粒细胞在内的致病免疫细胞的途径和优先激活。高压氧 治疗包括在大气压力增加的情况下呼吸100%的氧气以增加组织 氧合作用。在第二阶段的试验计划中，我们证明了这增加了粘膜的氧合。 组织导致溃疡性结肠炎疾病活动性的改善，炎性标志物的减少， 以及在急性红斑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局的影响 溃疡性结肠炎患者因急性症状住院通过多中心、双盲、假. 对照，3期临床试验。我们进一步的目标是探索高压氧通过 氧疗通过研究高压氧在2)上的特定效应来改善疾病活跃度 中性粒细胞和3)微生物组。高压氧治疗疗效的确认 将为溃疡性结肠炎的高危人群提供一种新的治疗方法 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、免疫系统和微生物群之间的相互作用。