L. Casei DG® in Patients With Irritable Bowel Syndrome.

Study Overview
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Brief Summary
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To assess the effect of L. casei DG® (Lactobacillus paracasei CNCMI1572; Enterolactis® plus) on abdominal symptoms and gut microbiota metabolism/composition in non constipated patients with IBS (Irritable Bowel Syndrome). Patients will be randomized to receive L. casei DG® capsules, b.i.d. for 12 weeks the a 4 weeks Follow Up period will follow.

Official Title
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L. Casei DG® (Lactobacillus Paracasei CNCMI1572) in the Treatment of Patients With Irritable Bowel Syndrome: a Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo Controlled Study.

Conditions
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IBS - Irritable Bowel Syndrome

Intervention / Treatment
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* Dietary Supplement: L.casei DG
* Dietary Supplement: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years and ≤ 65 years A positive diagnosis of non constipated IBS (i.e., IBS-D and IBS-M, both males and females), according to Rome IV criteria. A negative outcome of colonoscopy performed within 5 years before screening if patient is at least 50 years old, or if patient meet any of the following alarm features: Has a documented weight loss within the past 6 months; or Has nocturnal symptoms; or Has a familiar history of colon cancer; or Has blood mixed with their stool (excluding blood from hemorroids). Negative relevant additional screening or consultation whenever appropriate Ability to conform to the study protocol. Exclusion Criteria: Patients with IBS-C or IBS-U according to Rome IV criteria Presence of any relevant organic, systemic or metabolic disease (particularly significant history of cardiac, renal, neurological, psychiatric, oncology, endocrinology, metabolic or hepatic disease), or abnormal laboratory values that will be deemed clinically significant on the basis of predefined values, (i.e..liver or kidney functional levels 2-times greater than the upper reference values) Ascertained intestinal organic diseases, including celiac disease, food allergies or inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticular disease, infectious colitis, ischemic colitis, microscopic colitis). Previous major abdominal surgery. Active malignancy of any type, or history of a malignancy (patients with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years before study enrolment are also acceptable). Untreated food intolerance such as ascertained or suspected lactose intolerance, as defined by anamnestic evaluation or, if appropriate, lactose breath test. Use of probiotics or topical and/or systemic antibiotic therapy during the last month. Systematic/frequent use of contact laxatives. Pregnant females or females of childbearing potential in the absence of effective contraceptive methods. Inability to conform to protocol. Treatment with any investigational drug within the previous 30 days. Recent history or suspicion of alcohol abuse or drug addiction. Presence of red or white flags at the Rome IV Psychosocial Alarm Questionnaire for Functional gastrointestinal Disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L. casei DG®<br>Interventions: Lactobacillus paracasei CNCMI1572 (At least 24 billion live cells per capsule) 1 capsule, b.i.d. for 12 weeks | Dietary Supplement: L.casei DG<br>* (At least 24 billion live cells per capsule) 1 capsule, b.i.d. for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Interventions : capsules for oral use, indistinguishable from active product. 1 capsule, b.i.d. for 12 weeks | Dietary Supplement: PLACEBO<br>* 1 capsule, b.i.d. for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have a response in pain | Patients who record on ≥ 50% of the days a reduction of ≥ 30% from their average baseline score for their worst abdominal pain.The standard 11-point numeric rating scale (from 0=none to 10=worst possible pain) will be used to measure abdominal pain. | 12 weeks | 
| Proportion of patients who have a response in stool consistencies | Patients who record a stool-consistency score < 5 in the same days in which they record a reduction of ≥ 30% from their average baseline score for their worst abdominal pain .For abnormal defecation, stool frequency and form will be measured using the Bristol Stool Form Scale (BSFS). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Pain relief | reduction of ≥ 30% from baseline in the score for the worst abdominal pain on ≥ 50% of days | 16 weeks | 
| Evaluation of global symptom score | Improvement in the global symptom score: a score of 0 or 1, or an improvement ≥ 2 over the baseline score, on ≥ 50% of days | 16 weeks | 
| Relief of IBS symptoms | Adequate relief of IBS symptoms on ≥ 50% of the past weeks (a response of yes on ≥50% of the weeks to the following question: Over the past week, have you had adequate relief of your IBS symptoms?) | 16 weeks | 
| IBS-SSS score questionnaire (Severity Scoring System ) | To assess the severity of symptoms related to Irritable Bowel Syndrome, assessed at baseline and at the end of treatment after 12 weeks (it is considered clinically significant a score reduction of at least 50 points). The questionnaire is composed by five questions wich generate a maximum score of 100 each using prompted visual analogue scales, leading to a total possible score of 500. | 16 weeks | 
| Improvement in stool consistency | stool consistency score ≤ 5 assessed with BSFS (Bristol Stool Form Scale) BSFS evaluates stool form and consistency (score from 1=dry stool to 7=liquid stoo. The ideal stool is generally 3 or 4) | 16 weeks | 
| Satisfaction with treatment | Overall satisfaction with treatment assessed by VAS scale (Visual Analogue Scale) | 16 weeks | 
| Quality of life | Quality of life assessment by validated Short-Form 12 Items Health Survey (SF-12) on a scale of 0 to 100 | 16 weeks | 
| Intake of rescue medication | type and frequencies of rescue medication | 16 weeks | 
| gut microbiota composition | Evaluation of changes in the gut microbiota composition and the relative abundance of bacterial OTUs (Operational Taxonomic Unit). | 16 weeks | 
| Short Chain Fatty Acids (SCFA) | Evaluation of Short Chain Fatty Acids levels in fecal samples | 16 weeks | 
| Free Aminoacids | Evaluation of Free aminoacids levels in fecal samples | 16 weeks | 
| Biogenic Amines | Evaluation of biogenic amines levels in fecal samples | 16 weeks | 
| Gut permeability for zonulin | evaluation of serum levels of zonulin | 16 weeks | 
| Gut permeability for citrulline | evaluation of serum levels of citrulline | 16 weeks | 
| Gut permeability for PV-1 (Plasmalemma vesicle-associated) protein | evaluation of serum levels of PV-1 (Plasmalemma vesicle-associated) protein | 16 weeks | 
| L. casei DG® strain in the feces | the recovery of L. casei DG® strain in the feces | 16 weeks |