Effect of a Probiotic Formula on Reducing SIBO in IBS Patients

Study Overview
=================
Brief Summary
-----------------
This randomized study evaluates the effectiveness of the a probiotic formula, compared with the antibiotic rifaximin, in the treatment of Small Intestinal Bacterial Overgrowth (SIBO) in Irritable Bowel Syndrome (IBS) patients.

Detailed Description
-----------------
Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disease in which recurrent abdominal pain is associated with defecation or a change in bowel habits. Disordered bowel habits are typically present (ie, constipation, diarrhea, or a mix of constipation and diarrhea), as are symptoms of abdominal bloating/distention. IBS pathophysiology is multifactorial and may include alterations of the gut microbiota, food intolerances and Small Intestinal Bacterial Overgrowth (SIBO). However, SIBO is a distinct entity than IBS, as patients can present SIBO without IBS. SIBO is diagnosed based on objective tests (breath test or microbial culture of duodenal aspirate) while IBS is a functional syndrome, diagnosed on symptoms (Rome-IV criteria). A probiotic formula composed of strains Pediococcus acidilactici CECT 7483 and Lactobacillus plantarum CECT 7484 and CECT 7485 was previously shown to improve quality of life in patients with IBS. Rifaximin is a a non-absorbable antibiotic commonly used for the treatment of SIBO.

Official Title
-----------------
Efficacy of a Probiotic Formula in Reducing Small Intestinal Bacterial Overgrowth (SIBO) in Patients With Irritable Bowel Syndrome (IBS)

Conditions
-----------------
Irritable Bowel Syndrome, Small Intestinal Bacterial Overgrowth

Intervention / Treatment
-----------------
* Dietary Supplement: Probiotic
* Drug: Rifaximin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients diagnosed with IBS according to Rome IV criteria (Lacy et al. Gastroenterology 2016) and with SIBO according to North American Consensus (Rezaie et al., Am J Gastroenterol. 2017), providing Informed Consent. Patients taking set doses of Proton Pump Inhibitors (PPIs) or antispasmodics can be included. Exclusion Criteria: Use of antibiotics in the 4 weeks before study initiation. Use of probiotics in the 2 weeks before study initiation. Use of loperamide or other prokinetics in the week before study initiation. Use of Plantago ovata, lactulose or other laxans in the week before study initiation. Use of antidepressants. Suspicion or confirmed diagnose of coeliac disease, inflammatory bowel disease (IBD), symptomatic diverticulosis/diverticulitis, or endometriosis. Previous intestinal surgery, except appendectomy and herniorrhaphy. Short bowel syndrome or pancreatitis. Concomitant treatment with immunosuppressors, oncologic disease, severe cardiovascular disease, positive for HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV). Other conditions that can interfere with the effect of probiotic. Pregnant or lactating women.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>Treatment with probiotic formula | Dietary Supplement: Probiotic<br>* Probiotic (dietary supplement) administrated once daily (u.i.d) for 8 weeks (3 billion cfus per day)<br>|
| Other: Antibiotic<br>Treatment with antibiotic rifaximin | Drug: Rifaximin<br>* Antibiotic rifaximin consisting 400 mg capsules administrated twice daily (b.i.d) for 1week.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SIBO | SIBO evolution determined by changes in exhaled H2 and methane (CH4) levels after ingestion of lactulose (25 g) | 0 and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota | Intestinal microbiota composition studied by metagenomics analysis from faecal samples | 0 and 4 weeks | 
| IBS severity | Measurement of IBS severity by Irritable Bowel Syndrome-Severity Score (IBSSS), ranging from 0 to 500 (<75, remission; 75-175, mild; 175-300, moderate; >300, severe cases) | 0, 4 and 8 weeks | 
| Intestinal related anxiety | Measurement of gastrointestinal specific anxiety by Visceral Sensitivity Index (VSI), 15 questions rated from 1 to 6. Higher ratings represent greater severity (min score= 15, max score= 90). | 0, 4 and 8 weeks | 
| Global improvement after treatment | Measured with on one question with 7 possible answers: (1) much worse, (2) moderately worse, (3) slightly worse, (4) unchanged, (5) slightly better, (6) moderately better, or (7) much better. | 8 weeks |