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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03557788
Recruitment Status : Unknown
Verified May 2018 by National University Hospital, Singapore.
Recruitment status was:  Recruiting
First Posted : June 15, 2018
Last Update Posted : June 15, 2018
Sponsor:
Collaborator:
National University, Singapore
Information provided by (Responsible Party):
National University Hospital, Singapore

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.

Condition or disease Intervention/treatment Phase
Irritable Bowel Syndrome With Diarrhea Drug: Rifaximin Oral Tablet Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Changes in Microbiota and Metabolomic Profile Between Rifaximin Responders and Non-responders In Diarrhoea-Predominant Irritable Bowel Syndrome
Actual Study Start Date : May 7, 2018
Estimated Primary Completion Date : May 7, 2019
Estimated Study Completion Date : May 7, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diarrhea
Drug Information available for: Rifaximin

Arm Intervention/treatment
Experimental: Rifaximin
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
PO 550mg TDS for 2 weeks




Primary Outcome Measures :
  1. Change from baseline in IBS-SSS questionnaire [ Time Frame: 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) ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A subject will be eligible for inclusion in this study if he/she meets all of the following criteria:

    1. Chinese subjects between 21 to 65 years of age.
    2. 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".

    3. 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:

    1. Related to defecation
    2. Associated with a change in frequency of stool
    3. 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:
    1. Improvement with defecation
    2. Onset associated with a change in frequency of stool
    3. 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.
    4. 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.
    5. 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).
    6. Subject must maintain a stable diet for the duration of the study.
    7. Subject is capable of understanding the requirements of the study, is willing to comply with all study procedures, understands the language of the informed consent form, and is capable and willing to sign the informed consent form.

Exclusion Criteria:

  • A subject will not be eligible for inclusion in this study if he/she meets any of the following criteria:

    1. Subject has other forms of IBS (Constipation predominant, Alternating, or Mixed)
    2. Subject has failed to record at least 3 days of the daily diary assessments during the Screening Phase.
    3. 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
    4. 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
    5. Subject has diabetes (Type 1 or Type 2)
    6. History of surgery to remove a segment of the gastrointestinal tract or bariatric surgery for obesity, or cholecystectomy at any time
    7. Appendectomy within 2 months or other abdominal surgeries within 6 months before entry into the trial
    8. Subject has a positive stool test for Yersinia enterocolitica, Campylobacter jejuni, Salmonella, Shigella, ovum and parasites, and/or Clostridium difficile
    9. 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.
    10. Subject has current or recent history (within 12 months before signing informed consent) of drug, laxative or alcohol abuse
    11. Subject is pregnant or lactating
    12. Subject has a history of human immunodeficiency virus (HIV) or hepatitis (B or C)
    13. Subject has a history of abnormal thyroid function not controlled by thyroid medications
    14. 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
    15. Subject has known allergy to rifaximin or rifampin or excipients
    16. Subject has participated in an investigational drug or device study within the 30 days prior to signing informed consent
    17. Subject has active malignancy within the last 5 years (exceptions: basal cell carcinomas of the skin, or if female, in situ cervical carcinoma that has been surgically excised)
    18. Subject has ever taken Rifaximin prior to this study
    19. Antibiotics and probiotic consumption within the last1 month.
    20. Drugs that could alter GI transit time or microbiome, or bile acid sequestrants. These include antidiarrheals (eg, loperamide), narcotics, prokinetic drugs.

NOTE: Tricyclic antidepressants and serotonin re-uptake inhibitors are allowed if the subject is at stable doses for at least 6 weeks prior to signing informed consent and the dose will remain stable throughout the duration of the study.

Medication to be avoided

The following concomitant medications are to be avoided if possible, after initiation of the diary eligibility period and throughout the study:

  • Any experimental drugs
  • Probiotic supplements
  • Antibiotics
  • Antipsychotic drugs
  • Antispasmodics
  • Antidiarrheals (eg, loperamide and bismuth subsalicylate)
  • IBS drugs (e.g., Alosetron)
  • Lubiprostone
  • Narcotics (specifically opioid analgesics)
  • Prokinetic drugs
  • Warfarin
  • Nonsteroidal anti-inflammatory drugs are prohibited if used for the treatment of IBS

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03557788


Locations
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Singapore
Soh Yu Sen, Alex Recruiting
Singapore, Singapore
Contact: Alex Soh, MB BCh, MRCP, FAMS    +6567724354    alex_ys_soh@nuhs.edu.sg   
Sponsors and Collaborators
National University Hospital, Singapore
National University, Singapore
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Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT03557788    
Other Study ID Numbers: 2017/00977
First Posted: June 15, 2018    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National University Hospital, Singapore:
Rifaximin
Additional relevant MeSH terms:
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Irritable Bowel Syndrome
Syndrome
Diarrhea
Disease
Pathologic Processes
Signs and Symptoms, Digestive
Signs and Symptoms
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Rifaximin
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents