Efficacy of Liraglutide Therapy in Patients With an Ileal -Pouch Anal Anastomosis (IPAA) and Chronic High Bowel Frequency
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Mean % Reduction of Bowel Frequency in Percent of the Mean 7-day Bowel Frequency After 4 Weeks of Therapy on Liraglutide vs Placebo Compared to Baseline .
研究概览
简要总结
Patients with an ileal pouch-anal anastomosis(IPAA; pouch) due to refractory inflammatory bowel disease and increased bowel frequency in the absence of significant pouch inflammation will be randomized to liraglutide or placebo in a prospective cross over study.
详细描述
Randomized, double-blind, 2-period, placebo- controlled, crossover proof of concept study.
Ten patients with increased bowel frequency defined as bowel frequency > 8 bowel movements in 24 hours on at least 4 of 7 days/week and presence of high bowel frequency > 4 weeks despite adequate therapy for acute pouchitis or Crohn's like disease of the pouch will be randomized to either liraglutide or placebo treatment for 6 weeks (Period 1). Subjects will be randomized 1:1 to 1 of 2 treatment sequences, liraglutide-placebo or placebo-liraglutide, and receive either liraglutide or volume-matched placebo. After a wash-out period of at least 5 days (the half-life of liraglutide is 11-12 hours, thus the minimal washout period of 5 days is equal to 10 half-life's) patients will be crossed over to the other treatment arm (Period 2). Since high bowel frequency can result in significant malaise and dehydration, patients not responding to the respective therapies in period 1 may be crossed over after 4 weeks of therapy or in period 2 can be terminated early at week 4. The rationale behind the early termination is based on 2 open-label cohorts reporting the efficacy of liraglutide or exenatide in patients with high output ileostomies (the patient group the most comparable to the pouch patient population). Glucagon-like peptide- 1 (GLP-1) receptor agonist therapy even at the lowest dose showed an almost immediate effect reducing the ostomy output after 1-3 days in most patients.Thus, patients not responding to a 4-week therapy with a GLP-1receptor agonist are highly unlikely to respond if the therapy would be continued.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent will be obtained before any trial-related procedures
- •Age > 18 years
- •Patients with IPAA and bowel frequency > 8 bowel movements in 24 hours on at least 4 of 7 days/week and presence of high bowel frequency > 4 weeks despite adequate therapy for acute pouchitis or Crohn's like disease of the pouch
排除标准
- •Significant pouch inflammation defined as an endoscopic pouch disease activity index (PDAI ) ≥ 4
- •Known stricture of the ileo-anal anastomosis or afferent limb stricture
- •New onset of high bowel frequency in the setting of acute pouchitis
- •IPAA since < 6 months
- •Known Clostridium difficile pouchitis
- •Known clinically significant chronic nausea and/or vomiting in the past
- •Known type 1 or type 2 diabetes
- •History of or active neoplasia
- •Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- •Renal impairment defined as glomerular filtration rate (glomerular filtration rate < 30)
- •Clinically significant decompensated liver disease defined as elevation of aspartate aminotransferase , alanine transaminase or bilirubin > 2-fold the upper limits of normal (Primary Sclerosing Cholangitis with liver function tests (LFT's) <1.5 upper limits of normal can be included)
- •New York Heart Association class 3 or greater heart failure or recent (within 6 months) cardiovascular event
- •Prior history of pancreatitis
- •Prior treatment with a GLP-1receptor agonist
- •Known hypersensitivity to liraglutide or any product components
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
- •Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
- •Any disorder, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.
研究组 & 干预措施
Liraglutide then Placebo
Participants will be randomly assigned to 6-week Liraglutide treatment. Then after a 5-day washout, treatment will continue with 6 weeks of placebo.
干预措施: Liraglutide Pen Injector (Drug)
Liraglutide then Placebo
Participants will be randomly assigned to 6-week Liraglutide treatment. Then after a 5-day washout, treatment will continue with 6 weeks of placebo.
干预措施: Placebo Pen Injector (Drug)
Placebo then Liraglutide
Participants will be randomly assigned to 6-week placebo treatment. Then after a 5-day washout, treatment will continue with 6 weeks of Liraglutide.
干预措施: Liraglutide Pen Injector (Drug)
Placebo then Liraglutide
Participants will be randomly assigned to 6-week placebo treatment. Then after a 5-day washout, treatment will continue with 6 weeks of Liraglutide.
干预措施: Placebo Pen Injector (Drug)
结局指标
主要结局
Mean % Reduction of Bowel Frequency in Percent of the Mean 7-day Bowel Frequency After 4 Weeks of Therapy on Liraglutide vs Placebo Compared to Baseline .
时间窗: Baseline, Week 4 (treatment period 1) and week 10 (treatment period 2)
Mean percentage reduction of 7-day bowel frequency after 4 weeks of therapy on Liraglutide vs placebo compared to baseline (baseline is defined as the mean 7-day bowel frequency in a 7-day period during the screening period before week 0). Due to the cross-over design, the outcome is reported depending on randomization in treatment period 1 at week 4 and treatment period 2 at week 10 vs baseline.
次要结局
- Change in the 7 Day Mean Number of Day and Night Bowel Frequency at Week 4 and 6 vs Baseline on Liraglutide vs Placebo(Baseline, Week 4 and week 6 (treatment period 1) and week 10 and week 12 (treatment period 2))
- Discontinuation of Therapy in Each Treatment Arm(treatment period 1 before week 6 or treatment period 2 before week 12)
- Mean % Reduction of Bowel Frequency in Percent of the Mean 7-day Bowel Frequency After 6 Weeks of Therapy on Liraglutide vs Placebo Compared to Baseline.(Baseline, week 6 (treatment period 1) and week 12 (treatment period 2))