Intestinal Permeability and Intestinal Microbiota in Irritable Bowel Syndrome
Primary Purpose
Irritable Bowel Syndrome With Diarrhea
Status
Active
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
prescribing anapproved drug, examination
Sponsored by
About this trial
This is an interventional treatment trial for Irritable Bowel Syndrome With Diarrhea
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.
Sites / Locations
- Elena Poluektova
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
No Intervention
Arm Label
Group A
Group B
Group C
Control
Arm Description
a group of patients who, after the examination, were prescribed therapy with trimebutine 600 mg per day for 2 months
a group of patients who, after the examination, were prescribed therapy with rebamipide 300 mg per day for 2 months
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
healthy volunteers
Outcomes
Primary Outcome Measures
Severity of complaints
The severity of complaints is assessed using "7×7" (7 symptoms per 7 days) questionnaire and GSRS (Gastrointestinal Symptom Rating Scale)
Low-grade inflammation
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
Secondary Outcome Measures
Tight junction protein level
In biopsies of the small and large intestine, tight junction proteins levels are assessed by two-dimensional electrophoresis
Mucin-2 expression
The level of Mucin-2 expression in biopsies of the small and large intestine is assessed by immunohistochemistry
Serum zonulin
The level of the permeability marker, serum zonulin, is assessed by enzyme-linked immunosorbent assay using an ELISA test kit (Immundiagnostik AG, Bensheim, Germany)
Gut microbiome
The composition of the gut microbiota in feces is analyzed by 16S rRNA sequencing
Short-chain fatty acids
Short-chain fatty acid levels in feces are assessed by gas chromatography-mass spectrometry
Adverse events
Patients are notified of the need to report any adverse and unintended signs (any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product)
Quality of life (general health, limitation of activities, physical health problems, emotional health problems, social activities, pain, energy and emotions, social activities, general health)
Quality of life ((general health, limitation of activities, physical health problems, emotional health problems, social activities, pain, energy and emotions, social activities, general health) was assessed using the 36-Item Short Form Survey (SF-36) questionnaire
Severity of complaints
The severity of complaints is assessed using "7×7" (7 symptoms per 7 days) questionnaire and GSRS (Gastrointestinal Symptom Rating Scale)
Low-grade inflammation
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
Tight junction protein level
In biopsies of the small and large intestine, tight junction proteins levels are assessed by two-dimensional electrophoresis
Mucin-2 expression
The level of Mucin-2 expression in biopsies of the small and large intestine is assessed by immunohistochemistry
Serum zonulin
The level of the permeability marker, serum zonulin, is assessed by enzyme-linked immunosorbent assay using an ELISA test kit (Immundiagnostik AG, Bensheim, Germany)
Gut microbiome
The composition of the gut microbiota in feces is analyzed by 16S rRNA sequencing
Short-chain fatty acids
Short-chain fatty acid levels in feces are assessed by gas chromatography-mass spectrometry
Full Information
NCT ID
NCT05379036
First Posted
March 31, 2022
Last Updated
May 12, 2022
Sponsor
I.M. Sechenov First Moscow State Medical University
1. Study Identification
Unique Protocol Identification Number
NCT05379036
Brief Title
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
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 23, 2021 (Actual)
Primary Completion Date
May 31, 2022 (Anticipated)
Study Completion Date
May 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
I.M. Sechenov First Moscow State Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Irritable Bowel Syndrome With Diarrhea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
a group of patients who, after the examination, were prescribed therapy with trimebutine 600 mg per day for 2 months
Arm Title
Group B
Arm Type
Experimental
Arm Description
a group of patients who, after the examination, were prescribed therapy with rebamipide 300 mg per day for 2 months
Arm Title
Group C
Arm Type
Experimental
Arm Description
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
Arm Title
Control
Arm Type
No Intervention
Arm Description
healthy volunteers
Intervention Type
Drug
Intervention Name(s)
prescribing anapproved drug, examination
Other Intervention Name(s)
Trimedate, Rebagit
Intervention Description
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.
Primary Outcome Measure Information:
Title
Severity of complaints
Description
The severity of complaints is assessed using "7×7" (7 symptoms per 7 days) questionnaire and GSRS (Gastrointestinal Symptom Rating Scale)
Time Frame
change from baseline points of questionnaires at 2 months
Title
Low-grade inflammation
Description
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
Time Frame
change from baseline numbers of eosinophils and lymphocytes at 2 months
Secondary Outcome Measure Information:
Title
Tight junction protein level
Description
In biopsies of the small and large intestine, tight junction proteins levels are assessed by two-dimensional electrophoresis
Time Frame
change from baseline tight junction proteins levels at 2 months
Title
Mucin-2 expression
Description
The level of Mucin-2 expression in biopsies of the small and large intestine is assessed by immunohistochemistry
Time Frame
change from baseline level of Mucin-2 at 2 months
Title
Serum zonulin
Description
The level of the permeability marker, serum zonulin, is assessed by enzyme-linked immunosorbent assay using an ELISA test kit (Immundiagnostik AG, Bensheim, Germany)
Time Frame
change from baseline level of serum zonulin at 2 months
Title
Gut microbiome
Description
The composition of the gut microbiota in feces is analyzed by 16S rRNA sequencing
Time Frame
change from baseline composition of the gut microbiota in feces at 2 months
Title
Short-chain fatty acids
Description
Short-chain fatty acid levels in feces are assessed by gas chromatography-mass spectrometry
Time Frame
change from baseline short-chain fatty acid levels at 2 months
Title
Adverse events
Description
Patients are notified of the need to report any adverse and unintended signs (any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product)
Time Frame
2 months after the start of the study
Title
Quality of life (general health, limitation of activities, physical health problems, emotional health problems, social activities, pain, energy and emotions, social activities, general health)
Description
Quality of life ((general health, limitation of activities, physical health problems, emotional health problems, social activities, pain, energy and emotions, social activities, general health) was assessed using the 36-Item Short Form Survey (SF-36) questionnaire
Time Frame
change from baseline points of questionnaire levels at 2 months
Title
Severity of complaints
Description
The severity of complaints is assessed using "7×7" (7 symptoms per 7 days) questionnaire and GSRS (Gastrointestinal Symptom Rating Scale)
Time Frame
baseline
Title
Low-grade inflammation
Description
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
Time Frame
baseline
Title
Tight junction protein level
Description
In biopsies of the small and large intestine, tight junction proteins levels are assessed by two-dimensional electrophoresis
Time Frame
baseline
Title
Mucin-2 expression
Description
The level of Mucin-2 expression in biopsies of the small and large intestine is assessed by immunohistochemistry
Time Frame
baseline
Title
Serum zonulin
Description
The level of the permeability marker, serum zonulin, is assessed by enzyme-linked immunosorbent assay using an ELISA test kit (Immundiagnostik AG, Bensheim, Germany)
Time Frame
baseline
Title
Gut microbiome
Description
The composition of the gut microbiota in feces is analyzed by 16S rRNA sequencing
Time Frame
baseline
Title
Short-chain fatty acids
Description
Short-chain fatty acid levels in feces are assessed by gas chromatography-mass spectrometry
Time Frame
baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vladimir Ivashkin
Organizational Affiliation
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Elena Poluektova
City
Moscow
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Data disclosure is not permitted by the local ethics committee. For more information about the study, please contact the principal investigator.
Citations:
PubMed Identifier
34115808
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.
Results Reference
result
Links:
URL
https://www.gastro-j.ru/jour/article/view/437
Description
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.)
Learn more about this trial
Intestinal Permeability and Intestinal Microbiota in Irritable Bowel Syndrome
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