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，有相当大的费用 因急性发作住院期间产生的这些费用金额。相当大比例的 因急性发作而住院的溃疡性结肠炎患者将无法对静脉注射类固醇产生反应，需要 二线疗法，例如生物制剂和/或结肠切除术，可能与显着的发病率相关 和死亡率。正在住院或近期因急性发作住院的溃疡性结肠炎患者 由于耀斑风险极高，因此被排除在传统的 2 期和 3 期药物开发试验之外 进展到结肠切除术或再次入院。需要新颖、安全、有效的治疗方法来优化 这个高风险孤儿群体的结果。溃疡性结肠炎的一个特点是慢性肠粘膜病变 缺氧和炎症，伴随缺氧反应途径和优先功能障碍 激活致病性免疫细胞。高压氧治疗包括在高压下呼吸 100% 氧气 增加大气压力以增加组织氧合作用。在第二阶段试验计划中，我们证明了 粘膜组织氧合作用的增加可改善溃疡性结肠炎的疾病活动 结肠炎、炎症标志物减少以及预防进展为生物制剂或结肠切除术 因急性发作而住院。在当前提案中，我们的目标是 1) 确认高压氧的影响 通过多中心治疗因急性发作而住院的溃疡性结肠炎患者的疾病结果 双盲、假对照、3 期临床试验。我们进一步的目标是通过以下方式探索机制： 哪种高压氧疗法通过研究高压氧特异性来改善疾病活动性 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 疗法将为溃疡性结肠炎高危人群提供一种新的疗法，这些患者 传统上被排除在传统临床试验计划之外，同时也增进了我们对 疾病发病机制以及缺氧、免疫系统和微生物组之间的相互作用。

项目成果

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.

关于中重度溃疡性结肠炎入院期间和入院后合理使用类固醇和出院计划的建议：兰德公司适当性小组的结果。

• 发表时间: 2022-08-01
• 作者: Dulai, Parambir S;Rai, Victoria;Raffals, Laura E;Lukin, Dana;Hudesman, David;Kochhar, Gursimran S;Damas, Oriana M;Sauk, Jenny S;Levy, Alexander N;Sofia, M Anthony;Tuskey, Anne;Deepak, Parakkal;Yarur, Andres J;Afzali, Anita;Ananthakrishnan, A
• 通讯作者: Ananthakrishnan, A

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

用于研究炎症性肠病宿主-微生物相互作用的粪便多组学。

• 发表时间: 2022
• 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