Rifaximin Therapy vs Low FODMAP Diet In IBS

Study Overview
=================
Brief Summary
-----------------
Functional gastrointestinal disorders (FGIDs) are common and from the most recent global epidemiology study, an estimated 40% of the world population suffer from the condition. FGIDs cause significant morbidity to patients, despite not influencing mortality. IBS is among the most important functional gastrointestinal disorder with an estimated 3.8 to 9.2 % of the general population worldwide were affected by this disorder. Rifaximin (gut specific antibiotic) and low FODMAP diet (dietary based therapy) were proven to be effective in treating irritable bowel syndrome (IBS), however there was no head-to-head study comparing both treatments. This study will help doctors to understand the efficacy of different IBS/SIBO treatments. With the evaluation of factors that can predict treatment response, doctor could potentially treat IBS and SIBO more effectively in future. The purpose of the study is to compare the clinical symptoms and psychological improvement in patients with irritable bowel syndrome (IBS) after treatment with Rifaximin versus treatment with low FODMAP diet. The factors that is associated with treatment response will also be evaluated. In IBS patients with small intestinal bacterial overgrowth (SIBO), eradication rate of SIBO will be evaluated.

Official Title
-----------------
Rifaximin Therapy Versus Low FODMAP Diet In Irritable Bowel Syndrome: A Randomised Controlled Trial

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

Intervention / Treatment
-----------------
* Drug: Rifaximin
* Other: Low FODMAP diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients diagnosed with Irritable bowel syndrome using Rome III diagnostic criteria with Abdominal Pain/ Discomfort Intensity of weekly average of worst abdominal pain/ discomfort in past 24 hours score of ≥ 3.0 on a 0 to 10 point scale AND Stool Consistency of at least 2 days per week with at least one stool that has a consistency of Type 6 or Type 7 BSS or <3 CSBM per week Subject who can provide written informed consent and willingness to comply with the requirement of the protocol Able to communicate in English, Malay, or Mandarin languages Exclusion Criteria: Patients with known hypersensitivity or contraindication to Rifaximin Pregnant / breastfeeding women Patients who are on probiotics for the past 1 month Presence of family history of GI malignancy or alarm features suggested malignancy - e.g. Unintentional weight loss (≥ 10% of body weight in recent 6 months), GI bleeding History of gastrointestinal (GI) malignancy Patients with any hepatobiliary or pancreatic diseases Patients with severe depression, anxiety, or other psychological disorder Patients with any terminal disease Other conditions determined by the investigator to be inappropriate for this clinical study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Antibiotics<br> | Drug: Rifaximin<br>* Administration route: PO Rifaximin 400mg TDS for 2 weeks<br>|
| Active Comparator: Dietary based therapy<br> | Other: Low FODMAP diet<br>* Low FODMAP diet under dietitian guidance for 4 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with adequate relief of composite of abdominal symptom (pain/discomfort) and stool symptom (frequency/ consistency) after treatment. | Adequate relief was defined as self-reported relief of both symptoms (abdominal symptom and stool symptom) at least in week 2 or 4. (Subjects will be provided with self-reported questionnaires for week 2 and 4). For IBS-D, relief was defined as a decrease of at least 30% from baseline in weekly mean ratings of IBS-related abdominal pain or discomfort and a weekly decrease of at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline. For IBS-C, relief was defined as a decrease of at least 30% from baseline in weekly mean ratings of IBS-related abdominal pain or discomfort and an increase of 1 or more complete spontaneous bowel movement (CSBM) per week compared with baseline. For IBS-M, relief was defined as fulfilled both IBS-D and IBS-C symptom relief criteria. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who had relief was determined from the patients' weekly assessments of global IBS symptoms, bloating, abdominal pain/ discomfort, and stool consistency/ frequency after treatment with Rifaximin or low FODMAP diet | Rated on a 5-point scale: 2 = Significantly Relieved, 1 = Moderately Relieved, 0 = Unchanged, -1 = Moderately Worse, and -2 = Significantly Worse for at least 50% of the days in a week. Relief was defined as a score of either 2 (Significantly Relieved) or 1 (Moderately Relieved). | 4 weeks | 
| Symptom severity score improvement | The symptom severity was assessed by the IBS-symptom severity (IBS-SS) score from baseline to 4 weeks after initiation of treatment. Total scores ranging from 0 to 500 | 4 weeks | 
| Proportion of patients with SIBO who had eradication of SIBO after treatment | as measured by glucose hydrogen breath test | 6 weeks | 
| Assessment of factors that were associated with treatment response | Baseline characteristic (age, gender, ethnicity), IBS subtype (IBS-D, IBS-C IBS-mixed), and SIBO status (positive or negative) of patients who responded to treatment (based on primary outcome) will be compared to non-responder | 6 weeks | 
| Change in Health-Related Quality of Life (HRQOL) score | HRQOL will be assessed using EuroQol-5D (EQ-5D) instrument. Overall utility score (as mean value) was calculated with a range score from 0 (worst health scenario) to a maximum of 1.0 (best health scenario). | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IBS, Rifaximin, low FODMAP diet, SIBO