Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 32
- 试验地点
- 4
- 主要终点
- Change in Mucosal 5-ASA Concentration from Baseline to Morning Medication Administration to Night Medication Administration
研究概览
简要总结
The hypothesis of this study is that appropriate time of day of administration of oral, once daily 5-ASA therapy in alignment with the host circadian rhythms will improve subclinical inflammation and microbial structure/function and increase mucosal 5-ASA levels.
All subjects will be randomized to once daily 5-ASA medications at two different times of the day: between 06:00 - 10:00 h or 18:00 - 22:00 h. Three disease assessments will performed at: 1) enrollment just before randomization; 2) month 3, at the completion of first arm (Condition 1), and 3) month 6, after completion of the second arm (Condition 2). During these study time points, participants will be asked to complete questionnaires, track their 5-ASA medication usage, provide a stool sample, blood draw, urine test, collect saliva, wear a watch to measure sleep patterns, and complete a flexible sigmoidoscopy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study will include individuals that are;
- •M/F, 18-65 years of age
- •Ulcerative Colitis with Inactive Disease (Mayo Score ≤ 2; partial Mayo Score ≤ 1 with endoscopic score 0-1)
- •Subclinical inflammation stool calprotectin > 50 or CRP > mg/L above the upper limit of normal or PROMIS Fatigue Score ≥ 50)
- •Stable medications with no disease flares for the > 3 months,
排除标准
- •Study will not include individuals that are;
- •Active UC at enrollment (Mayo > 2 and/or sigmoidoscopy score of 2 or 3)
- •Regular use of suppositories or enemas within the last 3 months ORA: 20052807-IRB01 Date IRB Approved: 11/6/2023 Amendment Date: 4/7/2024 Protocol Version Date: 4/4/2024 7
- •Use of biologics or immunomodulatory medications ( i.e. infliximab, Adalimumab, azathioprine, Vedolizumab, methotrexate, etc.)
- •Prior ostomy or subtotal colectomy
- •Recent prednisone or antibiotic use in last 12 weeks
- •Major Depression identified as Beck Depression Inventory (score ≥21)
- •Restless leg syndrome (score ≥ 15 on the IRLS Study Group Rating Scale)
- •Sleep apnea (score high risk ≥ 2 or more categories on the Berlin Questionnaire)
- •Clinically significant diabetes (Hgb-A1c>7)
- •Regular use of medications that affect intestinal permeability, intestinal motility and/or NSAIDs 4 weeks prior to the study
- •Clinically significant cardiac, renal (creatinine > twice normal) or liver disease
- •Alcohol use disorder (AUDIT>8)
- •Chronic use of illicit drugs
- •Inability to sign an informed consen
研究组 & 干预措施
Morning Medication Administration
Subjects are directed to take their medication between 06:00 and 10:00.
干预措施: Chronotherapy (Behavioral)
Night Medication Administration
Subjects are directed to take their medication between 18:00 and 22:00.
干预措施: Chronotherapy (Behavioral)
结局指标
主要结局
Change in Mucosal 5-ASA Concentration from Baseline to Morning Medication Administration to Night Medication Administration
时间窗: 30 minute flexible sigmoidoscopy at Baseline, 30 minute flexible sigmoidoscopy at Morning Medication Administration, and 30 minute flexible sigmoidoscopy at Night Medication Administration
HPLC of tissue samples taken during flexible sigmoidoscopy at Baseline, Morning Medication Administration and Night Medication Administration
Change in Stool Calprotectin from Baseline to Morning Medication Administration to Night Medication Administration
时间窗: 10 minute stool collection at Baseline, 10 minute stool collection at Morning Medication Administration, and 10 minute stool collection at Night Medication Administration
ELISA
次要结局
- Change in Mayo Score from Baseline to Morning Medication Administration to Night Medication Administration(5 minute questionnaire at Baseline, 5 minute questionnaire at Morning Medication Administration, 5 minute questionnaire at Night Medication Administration)
- Change in Circadian Rhythms from Baseline to Morning Medication Administration to Night Medication Administration(Wrist Actigraphy Watch worn for two weeks at Baseline, two weeks at Morning Medication Administration, and two weeks at night medication administration)
- Change in Intestinal Permeability from Baseline to Morning Medication Administration to Night Medication Administration(24 hour urine collection at baseline, 24 hour urine collection at Morning Medication Administration, and 24 hour urine collection at Night Medication Administration)
- Change in Serum Cytokines from Baseline to Morning Medication Administration to Night Medication Administration(Single blood draw at baseline, single blood draw at Morning Medication Administration, and single blood draw at Night Medication Administration)
研究者
Ali Keshavarzian
Chief of the Section of Gastroenterology
Rush University Medical Center