Changes in Microbiota and Metabolomic Profile Between Rifaximin Responders and Non-responders In Diarrhoea-Predominant Irritable Bowel Syndrome

NCT03557788 | Completed Phase 4 DMC

• 1 other identifier: 2017/00977
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Irritable Bowel Syndrome (IBS) carries a high prevalence worldwide and imposes substantial economic burden on patients, healthcare systems and society. In recent years, dysbiosis of the gut microbiota and bile acid (BA) malabsorption have been identified as putative pathophysiological mechanisms. Bile acid metabolism and gut microbiota are closely related. When patients with IBS-D were compared to healthy subjects, total levels of faecal BAs do not differ, but increased faecal primary BAs and reduced secondary BAs have been repeatedly observed in patients with IBS-D, suggesting abnormal BA deconjugation. Rifaximin, a non-absorbable antibiotic, has been shown in a recent meta-analysis to produce a therapeutic clinical gain compared to other treatment options for IBS, including placebo, paralleled by a high safety profile. It is also now known that changes in fecal microbiota have been observed in patients with IBS who have responded positively to Rifaximin. The relationship between microbiota changes, metabolomics changes after Rifaximin is unclear. There is emerging data to suggest duodenal dysbiosis as a putative pathophysiology, which in one study, clustered together with salivary microbiota than with fecal microbiota. However, the oral microbiome in patients with IBS has never been explored, which could possibly explain the downstream observations of duodenal and fecal dysbiosis. The investigators aim to assess the changes in metabolomic and microbiota profile after Rifaximin treatment, between responders and non-responders. The investigators will also explore the oral microbiome in IBS patients, and assess its relationship with fecal microbiome between responders and non-responders.

Conditions

Irritable Bowel Syndrome With Diarrhea

Keywords

Rifaximin

Outcome Measures

Primary Outcomes (1)

• Change from baseline in IBS-SSS questionnaire

  Severity of IBS-D will be measured using IBS-SSS questionnaire, at baseline (visit 2) and at completion of 2 week course of Rifaximin (Visit 3) as well as 3 months after end of Rifaximin (Visit 4). A responder will be defined as a reduction of IBS-SSS by more than 50 points.

  Start of Rifaximin treatment (Visit 2, which is 1 week after first/screening visit), End of Rifaximin treatment (Visit 3, which is 2 weeks after Visit 2), and 3 months after end of treatment (Visit 4)

Study Arms (1)

Rifaximin

EXPERIMENTAL

Patients who receive PO Rifaximin 500mg TDS for 2 weeks. All patients will receive treatment to evaluate the effect of the intervention. This is a single-arm study.

Drug: Rifaximin Oral Tablet

Interventions

Rifaximin Oral Tablet DRUG

PO 550mg TDS for 2 weeks

Rifaximin

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chinese subjects between 21 to 65 years of age.
• Male or female Females of childbearing (reproductive) potential must have a negative serum pregnancy test at screening and agree to use an acceptable method of contraception throughout their participation in the study. Acceptable methods of contraception include double barrier methods (condom with spermicide jelly or diaphragm with spermicide), hormonal methods (oral contraceptives, patches or medroxyprogesterone acetate), or an intrauterine device (IUD) with a documented failure rate of less than 1% per year. Abstinence may be considered an acceptable method of contraception at the discretion of the investigator.
• Note: Females who have been surgically sterilized (eg, hysterectomy or bilateral tubal ligation) or who are postmenopausal (total cessation of menses for \>1 year) will not be considered "females of childbearing potential".
• Subject has IBS-D confirmed by the Rome III or IV diagnostic criteria below:
• a. Rome IV Criteria: i. Recurrent abdominal pain, on average, at least 1 day per week in the last 3 months, associated with 2 or more of the following criteria:
• <!-- -->
• Related to defecation
• Associated with a change in frequency of stool
• Associated with a change in form (appearance) of stool ii. Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis b. Rome III Criteria: i. Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with two or more of the following:
• <!-- -->
• Improvement with defecation
• Onset associated with a change in frequency of stool
• Onset associated with a change in form (appearance) of stool ii. Criterion fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis iii. "Discomfort" means an uncomfortable sensation not described as pain. iv. Pain/discomfort frequency of at least 2 days a week. c. IBS-Diarrhoea (IBS-D) i. Predominant bowel habits are based on stool form on days with at least one abnormal bowel movement. Subtyping based on at least 2 weeks of daily diary data is recommended, using the "25% rule." Subtyping established when the patient is evaluated off medications used to treat bowel habit abnormalities. Patients must have more than 25% of bowel movements with Bristol stool form types 6 or 7 and less than 25% of bowel movements with Bristol stool form types 1 or 2.
• Subject does not have adequate relief of IBS symptoms on the first day of screening (Day 0) and has an IBS-SSS of at least 300 out of 500.
• Subject had a colonic evaluation (either colonoscopy or CT Colonography) within the last 5 years as part of an evaluation for IBS or IBS symptoms (which excludes inflammatory or neoplastic disease).

You may not qualify if:

• Subject has other forms of IBS (Constipation predominant, Alternating, or Mixed)
• Subject has failed to record at least 3 days of the daily diary assessments during the Screening Phase.
• Subject has current evidence of duodenal ulcer, gastric ulcer, diverticulitis, or infectious gastroenteritis. Note: Subjects with gastroesophageal reflux disease controlled by stable doses of medication or diet are eligible to participate in the study
• Subject has a history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, celiac disease), GI malignancy, GI obstruction, gastroparesis, carcinoid syndrome, pancreatitis, amyloidosis, ileus or cholelithiasis
• Subject has diabetes (Type 1 or Type 2)
• History of surgery to remove a segment of the gastrointestinal tract or bariatric surgery for obesity, or cholecystectomy at any time
• Appendectomy within 2 months or other abdominal surgeries within 6 months before entry into the trial
• Subject has a positive stool test for Yersinia enterocolitica, Campylobacter jejuni, Salmonella, Shigella, ovum and parasites, and/or Clostridium difficile
• Subject who has psychiatric disorders which are not controlled ("controlled" is based on the Investigator's medical judgment); subjects with psychoses are excluded regardless of current therapy.
• Subject has current or recent history (within 12 months before signing informed consent) of drug, laxative or alcohol abuse
• Subject is pregnant or lactating
• Subject has a history of human immunodeficiency virus (HIV) or hepatitis (B or C)
• Subject has a history of abnormal thyroid function not controlled by thyroid medications
• Subject has unstable cardiovascular or pulmonary disease, categorized by a worsening in the disease condition that required a change in treatment or medical care within 1 month of randomization
• Subject has known allergy to rifaximin or rifampin or excipients

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• National University of Singapore: collaborator

Study Sites (1)

Soh Yu Sen, Alex

Singapore, Singapore

Location

MeSH Terms

Interventions

Rifaximin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: June 15, 2018
• Study Start: May 7, 2018
• Primary Completion: August 13, 2021
• Study Completion: August 13, 2021
• Last Updated: April 19, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)