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

摘要

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.