Clinical trial NCT05379036: Intestinal Permeability and Intestinal Microbiota in Irritable Bowel Syndrome
Official title: The Role of Intestinal Permeability and Intestinal Microbiota in the Development of the Irritable Bowel Syndrome and Functional Dyspepsia Symptoms
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Irritable Bowel Syndrome With Diarrhea
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
First posted: 2022-05-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* A man or woman aged 18-59.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Severity of complaints
timeFrame: change from baseline points of questionnaires at 2 months
measure: Low-grade inflammation
timeFrame: change from baseline numbers of eosinophils and lymphocytes at 2 months
Secondary outcomes:
measure: Tight junction protein level
timeFrame: change from baseline tight junction proteins levels at 2 months
measure: Mucin-2 expression
timeFrame: change from baseline level of Mucin-2 at 2 months
measure: Serum zonulin
timeFrame: change from baseline level of serum zonulin at 2 months
measure: Gut microbiome
timeFrame: change from baseline composition of the gut microbiota in feces at 2 months
measure: Short-chain fatty acids
timeFrame: change from baseline short-chain fatty acid levels at 2 months
measure: Adverse events
timeFrame: 2 months after the start of the study
measure: Quality of life (general health, limitation of activities, physical health problems, emotional health problems, social activities, pain, energy and emotions, social activities, general health)
timeFrame: change from baseline points of questionnaire levels at 2 months
measure: Severity of complaints
timeFrame: baseline
measure: Low-grade inflammation
timeFrame: baseline
measure: Tight junction protein level
timeFrame: baseline
measure: Mucin-2 expression
timeFrame: baseline
measure: Serum zonulin
timeFrame: baseline
measure: Gut microbiome
timeFrame: baseline
measure: Short-chain fatty acids
timeFrame: baseline
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Elena Poluektova
Study officials:
affiliation: I.M. Sechenov First Moscow State Medical University (Sechenov University)
name: Vladimir Ivashkin
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ivashkin V, Poluektov Y, Kogan E, Shifrin O, Sheptulin A, Kovaleva A, Kurbatova A, Krasnov G, Poluektova E. Disruption of the pro-inflammatory, anti-inflammatory cytokines and tight junction proteins expression, associated with changes of the composition of the gut microbiota in patients with irritable bowel syndrome. PLoS One. 2021 Jun 11;16(6):e0252930. doi: 10.1371/journal.pone.0252930. eCollection 2021.