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
• 负责人: Lauren Balmert Bonner
• 金额: $ 34.65万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10592029
• 关键词: Hyperbaric; Oxygen; Therapy; Ulcerative; Colitis

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. 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) immune 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.

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发作而住院，对静脉注射类固醇无效，并要求 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有关 和死亡率。因急性结肠炎而住院或最近住院的溃疡性结肠炎患者 传统的2期和3期药物开发试验因其风险太高而被排除在外 进行结肠切除术或再次入院。需要新的、安全的、有效的治疗方法来优化 在这一高危孤儿群体中的后果。溃疡性结肠炎的一个特征是慢性肠粘膜 低氧和炎症，伴随着低氧反应通路的功能障碍而优先 激活致病免疫细胞。高压氧治疗包括呼吸100%的氧气 增加大气压以增加组织的氧合。在第二阶段试验计划中，我们演示了 这种粘膜组织氧合的增加导致溃疡性疾病活动性的改善 结肠炎，炎性标志物的减少，以及防止进展为生物制剂或结肠切除术 因急性照明弹住院治疗。在目前的提案中，我们的目标是1)确认高压氧的影响 多中心治疗急性溃疡性结肠炎急性发作患者的疾病结局 双盲、假对照、3期临床试验。我们的进一步目标是通过以下方式探索这些机制 通过研究高压氧的特异性，哪种高压氧疗法可以改善疾病活动性 对2)免疫细胞和3)微生物组的影响。高压氧治疗效果的确认 治疗将为溃疡性结肠炎患者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。

项目成果

Recommendations on the Appropriate Management of Steroids and Discharge Planning During and After Hospital Admission for Moderate-Severe Ulcerative Colitis: Results of a RAND Appropriateness Panel.

• DOI: 10.14309/ajg.0000000000001775
• 发表时间: 2022-08-01
• 期刊: The American journal of gastroenterology

Stool multi-omics for the study of host-microbe interactions in inflammatory bowel disease.

• DOI: 10.1080/19490976.2022.2154092
• 发表时间: 2022-01
• 期刊: GUT MICROBES
• 影响因子: 12.2
• 作者: Sauceda, Consuelo;Bayne, Charlie;Sudqi, Khadijeh;Gonzalez, Antonio;Dulai, Parambir S.;Knight, Rob;Gonzalez, David J.;Gonzalez, Carlos G.
• 通讯作者: Gonzalez, Carlos G.