Morning Light Treatment for Inflammatory Bowel Disease: A Pilot Clinical Trial

晨光治疗炎症性肠病：初步临床试验

• 批准号: 10710708
• 负责人: Helen Julia Burgess
• 金额: $ 31.2万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10710708
• 关键词: Abdominal Pain; Adherence; Affect; Aftercare; Age; American; Biological; Biological Clocks; Biological Markers; Biological Products; Biopsy; Body Weight decreased; Chronic; Circadian Dysregulation; Clinic; Clinical; Clinical Trials; Colitis; Colonic inflammation; Conduct Clinical Trials; Crohn' s disease; Data; Development; Devices; Diarrhea; Disease; Disease remission; Fatigue; Fibromyalgia; Flare; Foundations; Frequencies; Future; Gastroenterology; Health system; Healthcare; Hemorrhage; Hour; Human; Immune Targeting; Impairment; Individual; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Intestines; Leukocyte L1 Antigen Complex; Light; Measures; Melatonin; Mental Depression; Michigan; Mission; Moods; National Institute of Diabetes and Digestive and Kidney Diseases; Operative Surgical Procedures; Participant; Patient Outcomes Assessments; Patients; Persons; Phototherapy; Quality of life; Questionnaires; Randomized; Rectum; Relapse; Restless Legs Syndrome; Risk Factors; Rodent; Sampling; Severity of illness; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Steroids; Symptoms; System; Testing; Therapeutic; Treatment outcome; Ulcerative Colitis; Universities; Wrist; actigraphy; affective disturbance; biological sex; chemically induced colitis; circadian; circadian pacemaker; cost estimate; depressive symptoms; disorder control; experience; gastrointestinal; gastrointestinal symptom; gut inflammation; improved; improvement on sleep; indexing; intervention effect; modifiable risk; novel; pain reduction; pain symptom; primary outcome; recruit; rectal; response; sex; side effect; sleep quality; standard measure; success; symptomatic improvement; systemic inflammatory response; targeted treatment; tissue injury; treatment as usual; treatment effect; treatment group

ABSTRACT Inflammatory bowel disease (IBD) is a disabling chronic inflammatory condition that includes two subtypes, ulcerative colitis (UC) and Crohn’s disease (CD). IBD causes gastrointestinal symptoms such as abdominal pain, rectal bleeding, and diarrhea, and extraintestinal symptoms such as sleep and mood disturbances. IBD affects over 3 million Americans and has a relapsing and remitting course with up to 50% of patients experiencing exacerbations each year. Immune targeted therapies such as biologics help control IBD, but patients continue to suffer from high rates of suboptimal disease control and extraintestinal symptoms such as fatigue, depression, and impaired quality of life. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity, which have minimal side effects, and are readily available and affordable. Circadian disruption (disruption of the “body clock”), is proinflammatory, worsens intestinal function, and is associated with increased disease activity, worse gastrointestinal and extraintestinal symptoms and impaired quality of life in IBD. Thus, circadian disruption may be an important modifiable treatment target for IBD. Morning light treatment, which advances (shifts earlier) and stabilizes circadian timing, may have potential to improve symptoms and disease severity in IBD. However, no studies have explored the potential therapeutic benefits of morning light treatment for IBD. Recently, we tested a 4- week, 1-hour daily morning light treatment in individuals with fibromyalgia (R21NR016930), using a commercially available wearable light device. We found the morning light treatment was feasible, reliably advanced and stabilized sleep timing, and significantly improved depression, sleep quality and quality of life (all p≤0.02), all with minimal side effects. Encouraged by this success, we propose to test the same morning light treatment in individuals with IBD, in response to PAS-20-160: Small R01s for Clinical Trials, which does not require preliminary data. Sixty-eight individuals with biopsy-proven IBD, clinically active disease and impaired IBD quality of life will be randomized to 4 weeks of morning light treatment (1 h/day) or 4 weeks of treatment as usual (TAU), with equivalent study contact in each group (completed sample n=50). Patient-reported outcomes (IBD quality of life, mood, sleep), clinician-rated disease severity, and a biomarker of gastrointestinal inflammation (fecal calprotectin) will be assessed before and after treatment. Aim 1 will determine the effect of morning light treatment versus TAU on patient-reported outcomes and Aim 2 will determine the effects on clinician-rated disease severity. We will also explore the effect of morning light treatment versus TAU on a biomarker of gastrointestinal inflammation (fecal calprotectin), and the potential moderating effects of steroid use, restless leg syndrome and biological sex. This project will be the first to test morning light treatment in people with IBD, and results will provide a foundation for developing morning light treatment as a novel non- pharmacological adjunctive treatment with potential to enhance existing treatment outcomes for IBD.

抽象的 炎症性肠病 (IBD) 是一种致残性慢性炎症性疾病，包括两种亚型： 溃疡性结肠炎（UC）和克罗恩病（CD）。 IBD 会引起胃肠道症状，例如腹部 疼痛、直肠出血和腹泻，以及睡眠和情绪障碍等肠外症状。炎症性肠病 影响超过 300 万美国人，高达 50% 的患者会出现复发和缓解的病程 每年都会经历病情恶化。生物制剂等免疫靶向疗法有助于控制 IBD，但 患者继续遭受高比例的疾病控制不佳和肠外症状，例如 疲劳、抑郁和生活质量下降。迫切需要开发辅助治疗 更好地管理 IBD 症状和疾病活动的方法，其副作用最小，并且 容易获得且负担得起。昼夜节律紊乱（“生物钟”紊乱）具有促炎性， 肠道功能恶化，并与疾病活动增加、胃肠道和胃肠功能恶化有关 IBD 的肠外症状和生活质量受损。因此，昼夜节律紊乱可能是一个重要的因素 IBD 的可修改治疗目标。晨光治疗，推进（提前移动）并稳定 昼夜节律，可能有改善 IBD 症状和疾病严重程度的潜力。然而，没有研究 探索了晨光治疗 IBD 的潜在治疗益处。最近，我们测试了 4- 每周，每天对纤维肌痛患者进行 1 小时晨光治疗 (R21NR016930)，使用 市售可穿戴照明设备。我们发现晨光治疗是可行的、可靠的 提前且稳定的睡眠时间，显着改善抑郁症、睡眠质量和生活质量（全部 p≤0.02），所有副作用都最小。受到这一成功的鼓舞，我们建议测试同一个晨光 针对 IBD 个体的治疗，响应 PAS-20-160：用于临床试验的小型 R01，该试验不 需要初步数据。 68 名经活检证实患有 IBD、临床活动性疾病且受损的个体 IBD 生活质量将随机分为 4 周晨光治疗（每天 1 小时）或 4 周治疗： 通常（TAU），每组具有同等的研究接触（完成的样本 n=50）。患者报告的结果 （IBD 生活质量、情绪、睡眠）、临床医生评定的疾病严重程度以及胃肠道生物标志物 将在治疗前后评估炎症（粪便钙卫蛋白）。目标 1 将决定效果 晨光治疗与 TAU 对患者报告结果的影响，目标 2 将确定对患者报告结果的影响 临床医生评定的疾病严重程度。我们还将探讨晨光治疗与 TAU 对 胃肠道炎症的生物标志物（粪便钙卫蛋白）以及类固醇的潜在调节作用 使用、不宁腿综合症和生物性别。该项目将是第一个在美国测试晨光处理的项目 患有 IBD 的人，研究结果将为开发晨光疗法作为一种新型的非治疗方法奠定基础。 药物辅助治疗有可能增强 IBD 的现有治疗效果。