Prevention of Ulcerative Colitis by Prebiotics: Efficacy and Protective Mechanisms
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 1
- 主要终点
- Prevention of relapse
研究概览
简要总结
Ulcerative colitis (UC) is a relapsing chronic intestinal inflammation with no existing cure, that affects over 300 per 100.000 Canadians, the highest prevalence in the world. The standard drug therapies are expensive and potentially toxic, and mostly directed against the chronic inflammatory process. UC is the result of a dysbiosis between disease-inducing and protective intestinal bacteria in a genetically susceptible host. Non-digestible dietary carbohydrates (NDC) stimulate the growth of protective endogenous intestinal bacteria which ferment them into short-chain fatty acids (SCFA), some of the latter with natural anti-inflammatory properties, and are called prebiotics. The investigator was the first to report that oral intake of NDC, the dietary β-fructans inulin plus fructo-oligosaccharides (FOS), reduced colitis in a genetically-induced rat colitis model. Both inulin and FOS reduced colitis, each NDC modifying specific luminal microbiota. A small trial with the same mixture of NDC in patients with active UC relapsing on oral 5-aminosalicylic acid (5-ASA) showed a dose-dependent clinical response, confirming the translational potential of this NDC mixture.
The investigators propose a randomized placebo-controlled trial to assess if inulin plus FOS can also prevent such relapses in UC patients with inactive disease on stable maintenance drugs. Primary hypothesis is that inulin plus FOS is effective adjunct therapy to standard drugs for maintaining clinical remission. The second hypothesis is that the colonic microflora and its metabolic function, altered by inulin plus FOS, or not, mediate protection or relapse in UC. The longitudinal design of this maintenance prevention study and by serially collecting colon biopsies, stool, serum and urine within the same patient before a relapse (inflammation) occurs, would enable to identify unique changes in the intestinal microbiota, their metabolic functions and also assess effects on host-immune response that are associated with remission or before a relapse occurs during treatment with beta-fructans, or not.
详细描述
Objectives: Based on the efficacy of inulin plus FOS shown in experimental colitis as well as their ability to improve active human UC the investigators propose double-blind placebo controlled study using Synergy1, a 1:1 FOS/ inulin mixture, in patients in clinical remission of UC. The specific aims of this study are as follow:
- To determine if β-fructans are effective in maintaining clinical remission in UC patients.
- To examine the mechanisms of action of β-fructans on the intestinal microbiota composition and function and host immune response of these patients.
It is hypothesized that β-fructans will prolong remission in UC patients with inactive disease maintained on standard drug therapy and that the prebiotics beneficial effect is associated with enhanced colonic energy homeostasis as a result of specific stimulation of butyrate- and/ or other SCFA-producing microorganisms combined with improved host mucosal energy and inflammation regulation.
The proposed trial
Trial Design: A double blind placebo controlled clinical trial
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with Ulcerative colitis (UC) with confirmed diagnosis by histology and endoscopy.
- •Currently in clinical remission defined as total Mayo score of ≤ 2 and endoscopic score of 0 or 1) who have experienced at least one flare in the past 18 months.
- •On stable doses of oral 5-ASA for 2 weeks and/or a stable doses of azathioprine and/or anti-tumor necrosis factor (anti-TNF) biologics for 2 months
- •Colonic involvement of >15 cm from the anal verge.
- •Ability to give valid informed consent
- •For females of child bearing potential, a negative pregnancy test and an agreement to use appropriate birth control over the study period.
排除标准
- •Crohn's disease, indetermined colitis or infectious colitis.
- •Active UC, (total Mayo score of ≥ 3)
- •Taking prednisone (or steroid equivalent) within 1 month of enrollment
- •Used topical 5-ASA or steroids within 2 weeks of enrollment
- •Using immunosuppressive treatments of 6-mercaptopurine or methotrexate
- •Used antibiotics within 2 months
- •Used anti-diarreal agents with the previous 3 days
- •Pregnancy or lactation
- •Significant chronic disorders such as severe cardiac disease, significant renal failure, severe pulmonary disease (need for oxygen)
- •Active gastrointestinal infection
- •Severe psychiatric disorder
- •Not able to consent to the study.
研究组 & 干预措施
Prebiotic
Prebiotic group will take 15 grams of prebiotic product Synergy-1 per day for 6 months. Synergy-1 is chicory-derived β-fructans inulin plus FOS (1:1). During the first two weeks the patient is advised to take 7.5 g of the product at breakfast only. Starting in week 3 until the end of the treatment the participant will take 7.5 g at breakfast and 7.5 g at dinner for a total of 6 months, or until you experience a flare.
干预措施: Synergy-1 (Dietary Supplement)
Placebo
Placebo group will take 15 grams of maltodextrin per day for 6 months. Maltodextrin is a sugar adsorbed in the small bowel with no effect on the colonic intestinal microbiota. During the first two weeks the patient is advised to take 7.5 g of the product at breakfast only. Starting in week 3 until the end of the treatment the participant will take 7.5 g at breakfast and 7.5 g at dinner for a total of 6 months, or until you experience a flare.
干预措施: Maltodextrin (Dietary Supplement)
结局指标
主要结局
Prevention of relapse
时间窗: 6 months
The percentage of patients that experienced relapse during the treatment period in prebiotic group versus that in the placebo group. Percentage will be calculated using the number of patients that relapse divided to the total number of patients in the treatment group. Relapse is defined as an total Mayo score of 3 or more with an endoscopy grade equal to or more than 2, and rectal bleeding for at least 3 days.
次要结局
- Changes in fecal calprotectin(0, 1, 3 and 6 month)
- Time to relapse(6 months)
- Patient compliance(3 and 6 month)
- Changes in partial Mayo score(0 and 6 month)
- Patient tolerability(3 and 6 month)
- Changes in endoscopic disease activity inflammation(0 and 6 month)