The Role of Intestinal Permeability and Intestinal Microbiota in the Development of the Irritable Bowel Syndrome and Functional Dyspepsia Symptoms
试验速览
- 阶段
- 4 期
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Severity of complaints
研究概览
简要总结
Patients with diarrhea-predominant irritable bowel syndrome (IBS) and functional dyspepsia (FD) were examined and received treatment in the study. Severity of complaints and quality of life patients were assessed according to questionnaires. The state of the intestinal barrier (analysis of the protein composition, intestinal mucin levels in biopsies, serum zonulin level in blood), the composition of the gut microbiota (16S rRNA gene sequencing), bacterial metabolic function (short-chain fatty acid levels in feces), and the presence of gut inflammation (levels of lymphocytes and eosinophils in biopsies) were assessed in the patients. Patients were divided into 3 treatment groups: trimebutin + placebo, rebamipide + placebo, trimebutin + rebamipide. The above parameters were compared in patients before and after treatment.
详细描述
The study included 60 patients with an established diagnosis IBS and FD. Patients were randomized in toone of three groups. Patients in group 1 received Trimedat (trimebutine, marketing authorization number LP-005534/07 of 2007-12-28) for 2 months, patients in group 2 received Trimedat and Rebagit (rebamipide, marketing authorization number LP-001831 of 2012-09-12) for 2 months, patients in group 3 received Rebagit for 2 months. The patients were blinded to the treatment assignment. At inclusion and 1 month after the severity of complaints were assessed, 2 months after starting treatment, the severity of complaints, quality of life, state of tight junction proteins, mucin-2 expression level, serum zonulin level, histological investigation of the mucous membrane of the small and large intestine, state of the intestinal microbiota and short-chain fatty acid levels were assessed. After the end of the study, an interim analysis of the effect of the therapy on the parameters was carried out. In the case of a positive effect, a full analysis of all the aforementioned factors contributing to its development was to be performed.
In addition, all these parameters were also in the control group (15 healthy volunteers without complaints, matched for sex and age with the main group).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent
- •A man or woman aged 18-
- •For women of childbearing age: mandatory use of contraceptive methods.
- •Confirmed diagnosis of IBS-D and functional dyspepsia by clinical, instrumental and blood chemistry findings (according to the Clinical Guidelines of the Russian Gastroenterological Association and the Russian Association of Coloproctologists (2016)
- •Absence of Helicobacter Pylori infection according to the urea breath test in the past 6 months before inclusion.
- •Ability to understand and willingness to comply with all protocol details.
排除标准
- •Prematurely discontinuation of the consumption of tested drugs/placebo;
- •Started taking antibiotics, other probiotics, or prebiotics during the follow-up period;
- •Refusal to participate during the follow-up period, including refusal to come for re-examination 2 months after inclusion;
- •Cancer or inflammatory bowel disease diagnosis during the follow-up period.
研究组 & 干预措施
Group A
a group of patients who, after the examination, were prescribed therapy with trimebutine 600 mg per day for 2 months
干预措施: prescribing anapproved drug, examination (Drug)
Group B
a group of patients who, after the examination, were prescribed therapy with rebamipide 300 mg per day for 2 months
干预措施: prescribing anapproved drug, examination (Drug)
Group C
a group of patients who, after the examination, were prescribed therapy with trimebutine 600 mg per day + rebamipide 300 mg per day for 2 months
干预措施: prescribing anapproved drug, examination (Drug)
结局指标
主要结局
Severity of complaints
时间窗: change from baseline points of questionnaires at 2 months
The severity of complaints is assessed using "7×7" (7 symptoms per 7 days) questionnaire and GSRS (Gastrointestinal Symptom Rating Scale)
Low-grade inflammation
时间窗: change from baseline numbers of eosinophils and lymphocytes at 2 months
In biopsies of the small and large intestine, numbers of eosinophils and lymphocytes in the field of view were assessed by histological examination with hematoxylin-eosin staining
次要结局
- Serum zonulin(baseline)
- Mucin-2 expression(baseline)
- Short-chain fatty acids(baseline)
- Adverse events(2 months after the start of the study)
- Low-grade inflammation(baseline)
- Severity of complaints(baseline)
- Tight junction protein level(baseline)
- Gut microbiome(baseline)
- Quality of life (general health, limitation of activities, physical health problems, emotional health problems, social activities, pain, energy and emotions, social activities, general health)(change from baseline points of questionnaire levels at 2 months)