Irritable Bowel Syndrome With DiarrheaPhase 4NCT05379036
Intestinal Permeability and Intestinal Microbiota in Irritable Bowel Syndrome
A Phase 4 study testing prescribing anapproved drug, examination in people with Irritable Bowel Syndrome With Diarrhea, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 59 yearsHealthy volunteers can take part
- Conditions the study is for
- Irritable Bowel Syndrome With Diarrhea
- What is being tested?
- prescribing anapproved drug, examination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteRussia
- Study dates
- 23 Jun 2021to 31 May 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Intestinal Permeability and Intestinal Microbiota in the Development of the Irritable Bowel Syndrome and Functional Dyspepsia Symptoms
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.
Read the 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
- Being tested
- prescribing anapproved drug, examination
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prescribing anapproved drug, examinationDrug
Also called Trimedate, Rebagit
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | a group of patients who, after the examination, were prescribed therapy with trimebutine 600 mg per day for 2 months Receives: Drug: prescribing anapproved drug, examination |
| Group B | Experimental | a group of patients who, after the examination, were prescribed therapy with rebamipide 300 mg per day for 2 months Receives: Drug: prescribing anapproved drug, examination |
| Group C | Experimental | 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 Receives: Drug: prescribing anapproved drug, examination |
| Control | No intervention | healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of complaints
The severity of complaints is assessed using "7×7" (7 symptoms per 7 days) questionnaire and GSRS (Gastrointestinal Symptom Rating Scale)
Measured: change from baseline points of questionnaires at 2 months
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
Measured: change from baseline numbers of eosinophils and lymphocytes at 2 months
Secondary outcomes (14)
Tight junction protein level
In biopsies of the small and large intestine, tight junction proteins levels are assessed by two-dimensional electrophoresis
Measured: change from baseline tight junction proteins levels at 2 months
Mucin-2 expression
The level of Mucin-2 expression in biopsies of the small and large intestine is assessed by immunohistochemistry
Measured: change from baseline level of Mucin-2 at 2 months
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)
Measured: change from baseline level of serum zonulin at 2 months
Gut microbiome
The composition of the gut microbiota in feces is analyzed by 16S rRNA sequencing
Measured: change from baseline composition of the gut microbiota in feces at 2 months
Short-chain fatty acids
Short-chain fatty acid levels in feces are assessed by gas chromatography-mass spectrometry
Measured: change from baseline short-chain fatty acid levels at 2 months
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)
Measured: 2 months after the start of the study
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
Measured: change from baseline points of questionnaire levels at 2 months
Severity of complaints
The severity of complaints is assessed using "7×7" (7 symptoms per 7 days) questionnaire and GSRS (Gastrointestinal Symptom Rating Scale)
Measured: baseline
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
Measured: baseline
Tight junction protein level
In biopsies of the small and large intestine, tight junction proteins levels are assessed by two-dimensional electrophoresis
Measured: baseline
Mucin-2 expression
The level of Mucin-2 expression in biopsies of the small and large intestine is assessed by immunohistochemistry
Measured: baseline
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)
Measured: baseline
Gut microbiome
The composition of the gut microbiota in feces is analyzed by 16S rRNA sequencing
Measured: baseline
Short-chain fatty acids
Short-chain fatty acid levels in feces are assessed by gas chromatography-mass spectrometry
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2022
- Study start23 Jun 2021
- Primary completion31 May 2022 (estimated)
- Study completion31 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel Syndrome With DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- I.M. Sechenov First Moscow State Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vladimir Ivashkin, Principal investigator, I.M. Sechenov First Moscow State Medical University (Sechenov University)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05379036
- Sponsor's protocol ID
- 116227
- Status last verified
- Mar 2022
- First submitted
- 31 Mar 2022
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data disclosure is not permitted by the local ethics committee. For more information about the study, please contact the principal investigator.
Publications
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.
PubMed 34115808
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Intestinal Permeability and Intestinal Microbiota in the Development of the Irritable Bowel Syndrome and Functional Dyspepsia Symptoms
- ClinicalTrials.gov ID
- NCT05379036
- Acronym / sponsor ID
- 116227
- Conditions
- Irritable Bowel Syndrome With Diarrhea
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (actual)
- Lead sponsor
- I.M. Sechenov First Moscow State Medical UniversityUniversity, hospital or other
- Study start
- 23 Jun 2021 (actual)
- Primary completion
- 31 May 2022 (estimated)
- Study completion
- 31 May 2022 (estimated)
- First posted
- 18 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: prescribing anapproved drug, examinationa group of patients who, after the examination, were prescribed therapy with trimebutine 600 mg per day for 2 months |
| Group B | Experimental | Drug: prescribing anapproved drug, examinationa group of patients who, after the examination, were prescribed therapy with rebamipide 300 mg per day for 2 months |
| Group C | Experimental | Drug: prescribing anapproved drug, examinationa group of patients who, after the examination, were prescribed therapy with trimebutine 600 mg per day + rebamipide 300 mg per day for 2 months |
| Control | No intervention | –healthy volunteers |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| prescribing anapproved drug, examinationAlso: Trimedate, Rebagit* 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. | Drug | Group A, Group B, Group C |
Primary outcome
Severity of complaints
Time frame: 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
Time frame: 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
14 secondary outcomes
Tight junction protein level
Time frame: change from baseline tight junction proteins levels at 2 months
Mucin-2 expression
Time frame: change from baseline level of Mucin-2 at 2 months
Serum zonulin
Time frame: change from baseline level of serum zonulin at 2 months
Gut microbiome
Time frame: change from baseline composition of the gut microbiota in feces at 2 months
Short-chain fatty acids
Time frame: change from baseline short-chain fatty acid levels at 2 months
Adverse events
Time frame: 2 months after the start of the study
Quality of life (general health, limitation of activities, physical health problems, emotional health problems, social activities, pain, energy and emotions, social activities, general health)
Time frame: change from baseline points of questionnaire levels at 2 months
Severity of complaints
Time frame: baseline
Low-grade inflammation
Time frame: baseline
Tight junction protein level
Time frame: baseline
Mucin-2 expression
Time frame: baseline
Serum zonulin
Time frame: baseline
Gut microbiome
Time frame: baseline
Short-chain fatty acids
Time frame: baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Results publication: PubMed 34115808Ivashkin 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.
- 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.)Link provided by the sponsor.
- Individual participant dataSharing planned: No. Data disclosure is not permitted by the local ethics committee. For more information about the study, please contact the principal investigator.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vladimir Ivashkin principal investigator
I.M. Sechenov First Moscow State Medical University (Sechenov University)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing prescribing anapproved drug, examination in people with Irritable Bowel Syndrome With Diarrhea, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severity of complaints (time frame: change from baseline points of questionnaires at 2 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05379036, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2022.