Intestinal Permeability and Intestinal Microbiota in Irritable Bowel Syndrome

NCT ID: NCT05379036

Last Updated: 2022-05-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-23
• Study Completion Date: 2022-05-31

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).

Conditions

Irritable Bowel Syndrome With Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group A

a group of patients who, after the examination, were prescribed therapy with trimebutine 600 mg per day for 2 months

Group Type: EXPERIMENTAL

prescribing anapproved drug, examination

Intervention Type: DRUG

• Blood test to assess serum zonulin levels;
• Esophagogastroduodenoscopyand colonoscopy with biopsy from the small and large intestine followed by histological examination;
• Stool sample collection to assess short-chain fatty acid levels and the composition of the gut microbiota.

Then the patients were prescribed therapy with the approved drug trimebutin (trimedat) with placebo or trimebutine with rebamipide or rebamipide with placebo for 2 months.

Group B

a group of patients who, after the examination, were prescribed therapy with rebamipide 300 mg per day for 2 months

Group Type: EXPERIMENTAL

prescribing anapproved drug, examination

Intervention Type: DRUG

• Blood test to assess serum zonulin levels;
• Esophagogastroduodenoscopyand colonoscopy with biopsy from the small and large intestine followed by histological examination;
• Stool sample collection to assess short-chain fatty acid levels and the composition of the gut microbiota.

Then the patients were prescribed therapy with the approved drug trimebutin (trimedat) with placebo or trimebutine with rebamipide or rebamipide with placebo for 2 months.

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

Group Type: EXPERIMENTAL

prescribing anapproved drug, examination

Intervention Type: DRUG

• Blood test to assess serum zonulin levels;
• Esophagogastroduodenoscopyand colonoscopy with biopsy from the small and large intestine followed by histological examination;
• Stool sample collection to assess short-chain fatty acid levels and the composition of the gut microbiota.

Then the patients were prescribed therapy with the approved drug trimebutin (trimedat) with placebo or trimebutine with rebamipide or rebamipide with placebo for 2 months.

Control

healthy volunteers

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

prescribing anapproved drug, examination

• Blood test to assess serum zonulin levels;
• Esophagogastroduodenoscopyand colonoscopy with biopsy from the small and large intestine followed by histological examination;
• Stool sample collection to assess short-chain fatty acid levels and the composition of the gut microbiota.

Then the patients were prescribed therapy with the approved drug trimebutin (trimedat) with placebo or trimebutine with rebamipide or rebamipide with placebo for 2 months.

Intervention Type: DRUG

Other Intervention Names

Trimedate, Rebagit

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

I.M. Sechenov First Moscow State Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vladimir Ivashkin

Role: PRINCIPAL_INVESTIGATOR

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Locations

Elena Poluektova

Moscow, , Russia

Countries

Russia

References

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.

Reference Type: RESULT

PMID: 34115808 (View on PubMed)

Related Links

https://www.gastro-j.ru/jour/article/view/437

Kovaleva A.L., Poluektova E.A., Shifrin O.S. Intestinal Barrier, Permeability and Nonspecific Inflammation in Functional Gastrointestinal Disorders. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(4):52-59. (In Russ.)

Other Identifiers

116227

Identifier Type: -

Identifier Source: org_study_id