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.

摘要 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引起胃肠道症状，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。IBD 影响了300多万美国人，有高达50%的患者复发和缓解病程 每年都在经历病情恶化。免疫靶向治疗，如生物制剂，有助于控制IBD，但 患者继续遭受疾病控制率较高和肠外症状的困扰，如 疲劳、抑郁和生活质量受损。迫切需要发展辅助治疗 更好地管理IBD症状和疾病活动的方法，副作用最小，并且 随手可得，价格实惠。昼夜节律紊乱(打乱“生物钟”)，是促炎性的， 恶化肠道功能，并与疾病活动增加，胃肠道和 IBD患者的肠外症状和生活质量受损。因此，昼夜节律的扰乱可能是一个重要的 IBD的治疗目标可修改。晨光治疗，提前(提前)和稳定 昼夜节律，可能有可能改善IBD的症状和疾病严重程度。然而，没有研究表明 探索了晨光疗法对IBD的潜在治疗益处。最近，我们测试了一款4- 纤维肌痛患者的每周、每天1小时的晨光治疗(R21NR016930)，使用 市面上有可穿戴式照明设备。我们发现晨光治疗是可行的，可靠的 提前和稳定的睡眠时间，显著改善抑郁症、睡眠质量和生活质量(所有 P≤0.02)，所有的副作用都很小。受到这一成功的鼓舞，我们建议测试同样的晨光 对炎症性肠病患者的治疗，对PAS-20-160的反应：临床试验的小R01，它不起作用 需要初步数据。68名经活检证实为IBD、临床活动性疾病和受损的患者 IBD的生活质量将随机分为4周的晨光治疗(1小时/天)或4周的治疗 通常(TAU)，每组有等量的研究联系人(完成样本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，以及胃肠道的生物标记物 治疗前后将对炎症(粪便钙保护素)进行评估。目标1将决定 晨光治疗与TAU对患者报告的结果和目标2的影响将确定 临床医生评定的疾病严重程度。我们还将探索晨光处理与TAU相比对 胃肠道炎症的生物标记物(粪便钙保护素)以及类固醇的潜在缓和作用 使用，不宁腿综合症和生物性行为。该项目将是第一个测试晨光处理的项目 结果将为开发晨光治疗作为一种新型的非传染性疾病提供基础。 有潜力提高IBD现有治疗结果的药物辅助治疗。