Identification of the Microbiota (Gut Flora) Dependent Response to Rifaximin in Irritable Bowel Syndrome Patients

Phase 1

• Conditions: Irritable Bowel Syndrome; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2013-000357-41-IE
• Lead Sponsor: The Alimentary Pharmabiotic Centre, University College Cork

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-19
• Last Update Posted: 29 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Male or female subjects aged 18 and < 65 at the time of the screening visit.
2. IBS as defined by Rome III criteria.
3. Clinical laboratory tests at screening showing no clinically significant abnormalities in the opinion of the Investigator.
4. Signed and dated written informed consent prior to admission to the study.
5. Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
6. Female subject is currently either of:
• non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or any female who is surgically sterilized (via documented hysterectomy or bilateral tubal ligation). (For purposes of this study, postmenopausal is defined as one year without menses)
OR
• child bearing potential, the subject is eligible to enter and participate in this study if she is not lactating and has a negative pregnancy test both at screening (serum ?-HCG negative) and baseline (urine) prior to investigational product administration at visits 2, follow up on visits 3 and 4. The subject must also agree to one of the following methods of contraception:
i. Complete abstinence from intercourse two weeks prior to administration of study drug, throughout the clinical trial, until the completion of follow-up procedures or for two weeks following discontinuation of the study medication in cases where subject discontinues the study prematurely. (Subjects utilizing this method must agree to use an alternate method of contraception if they should become sexually active and will be queried on whether they have been abstinent in the preceding 2 weeks when they present to the clinic for the Final Visit.) or,
ii. Has a male sexual partner who is surgically sterilized prior to the Screen Visit and is the only male sexual partner for that subject or,
iii. Sexual partner(s) is/are exclusively female or,
iv. Oral contraceptives (either combined or progestogen only) with double-barrier method of contraception consisting of spermicide with either condom or diaphragm. (Women of child-bearing potential using an oral contraceptive in combination with a double-barrier method of contraception are required to continue to use this form of contraception until the end of their oral contraceptive pill packet following discontinuation of study medication).
v. Use of double-barrier contraception, specifically, a spermicide plus a mechanical barrier (e.g. male condom, female diaphragm). The subject must be using this method for at least 1 week following the end of the study or,
vi. Use of any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per year. The subject must have the device inserted at least 2 weeks prior to the first Screen Visit, throughout the study, and 2 weeks following the end of the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. As a result of any of the medical interview, physical examination, evaluation of mental state and psychiatric history or screening investigations the physician responsible considers the subject unfit for the study.
2. Subjects who are pregnant or nursing.
3. Evidence of a biochemical or structural abnormality of the digestive tract. These conditions include (but not limited to):
Current evidence, or history of (at any time in the past);
•inflammatory bowel disease (Crohn's disease or ulcerative colitis)
•Lactose intolerance, not on a stable diet
•Celiac Disease
•laxative abuse (in the clinical judgement of the physician)
•gastrointestinal surgery (exceptions include 6 months post-surgery for appendectomy, cholecystectomy, fundoplication without gas bloat, or hiatal hernia repair; 3 months post-surgery for herniorrhaphy without bowel resection)
•gastroparesis
•GI malignancy
•carcinoid syndrome
•amyloidosis
•chronic pancreatitis
•symptomatic gastrointestinal adhesions
•toxic megacolon
•gastrointestinal perforation
•gastrointestinal obstruction and/or stricture.
4. Current evidence of or occurrence within the past 6 months of:
•diverticulitis
•ileus
•symptomatic cholelithiasis
•proctitis.
5. Subjects who have taken any medication for the treatment of IBS within 1 month prior to screening except for anti-diarrhoeal medications or laxatives for control of bowel habit which are allowed if at a stable dose for 2 weeks prior to randomisation.
6. Subject is currently taking any prohibited medication, including antibiotics (within 3 month prior to screening)
7. Subjects who are taking NSAIDs including aspirin on a regular basis or within 48 hours of a study day.
8. Systemic or inhaled corticosteroids (Note: topical (e.g. nasal steroid) are allowed).
9. The subject has received an investigational drug or participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
10. History or presence of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
11. Any other clinically significant laboratory abnormality.
12. Any evidence of or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or in situ uterine cervix cancer that has been resected) within the previous 5 years.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Identification of a microbial signature associated with Responders versus Non Responders to treatment with Rifaximin.<br><br>(Response is defined as improved IBS symptoms which will be measured using an IBS symptom severity score and food frequency questionnaires between visits.);Secondary Objective: Identification of microbiome changes that are associated with an alleviation of symptoms.;Primary end point(s): The placebo effect in the IBS dataset is expected to affect 30% of the individuals. ;Timepoint(s) of evaluation of this end point: For all end points at end of Trial.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 70% of the dataset of 80 IBS subjects is expected to provide a true biological signal;Timepoint(s) of evaluation of this end point: For all endpoints at end of trial.