A Multistrain Probiotic in Patients With Irritable Bowel Syndrome With Predominant Constipation (EPORE)

Effect of a Mixture of Probiotics (Lactibiane Reference) in Patients With Irritable Bowel Syndrome Predominantly Constipation and Assessment of a Potential Biomarker (Resolvin D1): an Exploratory Study

Probiotics efficacy is mainly assessed by subjective endpoints such as the FDA responder rate or global relief, which partly explain contradictory results obtained in clinical trials with probiotic bacteria. Objective biomarkers of IBS will allow to measure the efficacy of probiotics. In the case of IBS-C, serum resolvin-D1 appears to be an interesting candidate due to its non-invasive and discriminating character compared to a healthy population. It is, inversely correlated with the severity of symptoms. Resolvin-D1 modulates the duration and intensity of inflammation by regulating the transcription of cytokines, chemokines and their receptors as well as other proteins involved in inflammation. Resolvin D1 could serve as a predictor of probiotic response based on its baseline value.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Constipation
• Intervention / Treatment: Dietary supplement: Probiotics mixture

Detailed Description

Resolvin D1 levels will be measured in patients with IBS-C as defined by the Rome IV criteria before 6 and 12 weeks after supplementation with a mixture of probiotics. The progression of IBS-C symptoms will also be assessed throughout the study.

The correlation with resolvin D1 levels and the severity of IBS symptoms will be investigated. The efficacy of the probiotic mixture in relieving the symptoms of IBS-C will be measured and compared based on the levels of resolvin D1.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bourgogne
    • Dijon, Bourgogne, France, 21000
      • CEN Nutriment

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Irritable Bowel Syndrome with constipation (IBS-C) according to Rome IV criteria ;
• IBS-SSS between 175-300 in the last 10 days ;
• Have experienced abdominal pain ≥ 40 according to the IBS-SSS questionnaire (abdominal pain item) during the last 10 days ;
• Whose abdominal pain / discomfort has had a significant impact on daily life during the past 10 days (impact ≥2 on a 5-point likert scale (from 0: no impact to 5: extreme impact) ;
• Ability to understand instructions and complete questionnaires Nurstrial APP.
• Affiliate or beneficiary of a social security ;
• Having given their free, informed and written consent.

Exclusion Criteria:

• CPRu > 10 mg/l
• Pregnant or breastfeeding woman, woman planning a pregnancy during the study period ;
• Intolerance or proven food allergy ;
• BMI <18.5 kg / m2 or BMI> 35 kg / m2 ;
• Diagnosis or known history of IBS-D, IBS-M, or unclassified forms of IBS, or other gastrointestinal pathologies ;
• With current first-line IBS-C treatment or second-line treatment ;
• alternative non pharmacological treatment ;
• Drug treatment affecting visceral sensitivity or intestinal transit ;
• dietary modification (exclusion of FODMAPs, prebiotic) or lifestyle ;
• Excessive smoking or drinking ;
• Having or planning bariatric surgery,
• With known pathologies affecting gut function ;
• With a deviant eating behavior,
• Treated with antibiotics in the 3 months preceding inclusion,
• Under legal protection,
• Already included in a clinical trial,
• With severely impaired physical/psychological health may affect study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Probiotics mixture; Daily supplementation with a mixture of probiotics for 12 weeks	Dietary supplement: Probiotics mixture; 12 weeks of daily supplementation with 1 g of probiotics mixture (4.10exp9 colony forming unit/g) containing: Bifidobacterium longum LA 101; Lactobacillus helveticus La 102; Lactococcus lactis LA 103; Streptococcus thermophilus LA 104

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the severity of IBS-C symptoms	Measured by the composite IBS-SSS (Irritable Bowel Syndrome-Severity Scale Scoring) system, compared to the baseline IBS-SSS value. Minimum : 0 (best condition) to maximum (worse condition): 500	At weeks 0, 4, 8 and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the severity of addominal pain	Mesured by the Abdominal pain domain of the IBS-SSS (Irritable Bowel Syndrome-Severity Scale Scoring) score compared to the baseline. Minimum (best condition) : 0 to maximum (worse condition): 100	At weeks 4, 8 and 12
Change of the number of days with abdominal pain	Mesured by the Number of days with abdominal pain domain of the IBS-SSS (Irritable Bowel Syndrome-Severity Scale Scoring) score compared to the baseline. Minimum (best condition) : 0 to maximum (worse condition): 100	At weeks 4, 8 and 12
Change of the severity of abdominal distension (bloating)	Mesured by the bloating-distension domain of the IBS-SSS (Irritable Bowel Syndrome-Severity Scale Scoring) score compared to the baseline. Minimum (best condition) : 0 to maximum (worse condition): 100	At weeks 4, 8 and 12
Change of the satisfaction with bowel habits	Mesured by the satisfaction with bowel habits domain of the IBS-SSS (Irritable Bowel Syndrome-Severity Scale Scoring) score compared to the baseline. Minimum (best condition) : 0 to maximum (worse condition): 100	At weeks 4, 8 and 12
Change of the IBS-related quality of life	Mesured by the IBS related quality of life domain of the IBS-SSS (Irritable Bowel Syndrome-Severity Scale Scoring) score compared to the baseline. Minimum (best condition) : 0 to maximum (worse condition): 100	At weeks 4, 8 and 12
Global assessment of symptoms relief	Measured by the Subject's Global Assessment (SGA) of Relief, compared to the baseline	At weeks 4, 8 and 12
Change of Resolvin-D1 levels	Blood measurement of resolvin-D1 compared to the baseline	At weeks 8 and 12
Change of CPRu (C Reactive Protein-ultrasensitive) levels	Blood measurement of C Reactive Protein ultrasensitive compared to the baseline	At weeks 8 and 12
Change of the intestinal microbiota	Biological parameter : Fecal microbiota measured by 16S rRNA gene sequencing compared to baseline	At weeks 6 and 12
Change of the stool frequency	Patient-reported number of stools using an e-diary, compared to baseline	At weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12
Change of the stools consistency	Patient-reported stools consistency by the Bristol Stool Scale, using an e-diary, compared to baseline	At weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12
Change of the Quality of Life	Measured by Medical Outcomes Study Short-Form General Health Survey Short Form-12 compared to baseline	At weeks 4, 8 and 12
Change of number of drugs consumption to alleviate the IBS-C symptoms	Patient-reported drug (laxative, spasmolytics) consumption using an e-diary, compared to baseline	At weeks 4, 8 and 12
Assessing the relationship between resolvin D1 levels and symptoms severity mesured by IBS-SSS symptoms scores	Regression analysis	At week 12
Assessing the relationship between baseline resolvin D1 levels and response to the probiotics supplementation measured by the responders rate (outcome 17)	Regression analysis	At week 12
Assessing the responders rate	Number of patients with a decrease in the weekly average of worst abdominal pain in the past 24 hours score (measured daily) of at least 30 percent compared with baseline weekly average and a stool Frequency Weekly Responder is defined as a patient who experiences an increase of at least one complete stool bowel movement per week from baseline.	At weeks 4, 8 and 12
Assessing the relationship between baseline microbiota and response to the probiotics supplementation measured by the responders rate (outcome 17)	Regression analysis	At week 12
Assessing the tolerance of the probiotics mixture	Adverse reactions analysis	At weeks 6 and 12
Assessing the global improvement	Measured by the patient global impression of improvement	At weeks 4, 8 and 12
Assessing the satisfaction regarding the mixture of probiotics	Measured by a 5 points Likert scale 0 : worse satisfaction to 5 : better satisfaction	At weeks 4, 8 and 12

Collaborators and Investigators

• Sponsor: CEN Biotech
• Collaborators: PiLeJe
• Investigators: Study Director: GABRIEL PERLEMUTER, PR, Hospital Antoine-Béclère

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2022
• Primary Completion (Actual): December 9, 2022
• Study Completion (Actual): December 9, 2022

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Constipation
• Other Study ID Numbers: C1674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No