Rifaximin for the Treatment of Irritable Bowel Syndrome
Information source: Cedars-Sinai Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Irritable Bowel Syndrome
Intervention: Rifaximin (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Cedars-Sinai Medical Center Official(s) and/or principal investigator(s): Mark Pimentel, MD, Principal Investigator, Affiliation: Cedars-Sinai Medical Center
Summary
We have recently shown that the majority of patients with irritable bowel syndrome (IBS)
have an abnormal lactulose breath test to suggest the presence of bacterial overgrowth of
the small intestine. In open label and double blind treatment of IBS subjects with
antibiotics, a dramatic improvement in clinical symptoms are observed. In these studies, the
antibiotic chosen was neomycin, which is noted to have an efficacy of 20-25% in normalizing
the lactulose breath test. A more efficacious antibiotic is needed. Therefore the aim of
this study is to determine the efficacy of rifaximin in normalizing the lactulose breath
test in IBS subjects with concomitant improvement in clinical symptoms.
Clinical Details
Official title: Rifaximin in the Treatment of Small Intestinal Bacterial Overgrowth and IBS: Double Blind Randomized Controlled Trial (Multicenter Trial)
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: Global improvement in IBS
Secondary outcome: Improvement in abdominal pain, diarrhea, constipation and bloating
Detailed description:
1. Rome I criteria positive IBS subjects will be enrolled in the study after inclusion and
exclusion criteria (see below for description of inclusion and exclusion criteria) are
applied. There will be no preference given to constipation or diarrhea predominant
forms of the condition.
2. Subjects will have a 7-day run in phase during which bowel movement consistency and
number will be recorded (see Appendix A for bowel movement record).
3. At the end of the 7-day run in, subjects will present after a 12 hour fast for a
lactulose breath test.
4. Prior to breath testing, subjects will be asked to fill out a symptom questionnaire
(Appendix B) based on the previous 7 days. Completion of the questionnaire is expected
prior to starting the breath test to prevent symptoms from the lactulose interfering
with the testing.
5. Subjects will then provide a baseline breath sample after which 10g of lactulose will
be administered. Breath samples will then be obtained every 15 minutes for 180 minutes.
The test will be plotted graphically and sealed by the technician in an envelope. The
subject and the investigators will be blinded to the results of the test. See below for
details of the breath testing.
6. Subjects will then be randomized to receive either placebo or rifaximin (400 mg tid)
for 10 days. Compliance will be tested by pill count.
7. On completion of the treatment, bowel movement consistency and number will again be
recorded for 7 days.
8. 7 days after completion of the antibiotic or placebo, subjects will return for a follow
up questionnaire (Appendix C) and breath test.
9. Subjects will then be sent a weekly questionnaire for a period of 2 months. During the
final 7 days of the 2 months, the bowel movement consistency and number will be tracked
again.
SPECIFIC METHODS:
Subject selection and enrollment:
Subjects will be selected for all studies based on the Rome I criteria (36). This will be
the preferred method of identifying IBS patients to avoid pre-selecting patients with C-
IBS. The goal is to evaluate methane as the determinant of transit, not constipation or
diarrhea symptoms as through Rome II criteria (37). All subjects who are receiving a
prokinetic drug at the time of enrollment will need to have a washout period of 7 days
before starting the study protocol. Subjects will be identified through advertising in
printed media and through the clinical operations of the GI motility program at Cedars-Sinai
Medical Center.
Exclusion Criteria:
Subjects with a history of inflammatory bowel disease (38), diabetes (39), previous
intestinal surgery (40-42), cirrhosis (43-47), celiac disease, probiotic use, current proton
pump inhibitor use (48-54), recent antibiotic use (past 3 months), history of bowel
obstruction (55), narcotic use (56) or age greater than 65 years (57-63) will be excluded.
Most of these conditions are known to influence enteric bacteria levels. Women of
childbearing years will undergo pregnancy testing before participating in the study (See
below for details on the pregnancy test used). Women with positive pregnancy tests will be
excluded.
Lactulose Breath test (LBT):
Subjects will present to the GI Motility clinic after a 12 hour fast. After a baseline
breath sample and ingestion of 10g-lactulose syrup (Inalco Spa, Milano, Italy, packaged by
xactdose Inc., South Beloit, IL), end-alveolar breath samples will be taken every 15 minutes
for a three hours. Breath samples will be analyzed using a model SC Quintron gas
chromatograph (Quintron Instrument Company, Milwaukee, WI) which determines breath hydrogen
and methane concentration in parts per million (ppm). Subjects will not be allowed to smoke
or exercise within 2 hours prior to performing the test (64). Methane exchanges quickly
across the alveolar membrane, so hyperventilation can falsely lower the concentration in
breath. Subjects will also be required to sit for the duration of the breath test such that
exertion will not increase alveolar clearance of this gas. If modest hyperventilation
occurs, the concentration of carbon dioxide in the breath sample will be used to correct for
quality of alveolar sampling. Note that in the clinical study breath test results will be
blinded to the investigator and patient to avoid influencing the interpretation of transit
and serotonin levels.
Questionnaires:
Three questionnaires will be used in this study. The first is a Stool Form and Frequency
Questionnaire (SFFQ). This questionnaire will be designed to determine the consistency of
the stool based on standard consistency plots. The second questionnaire is designed to
determine the duration and degree of IBS symptoms on visual analogue scores. This
questionnaire is specifically administered before the first breath test and is designed to
determine baseline symptoms and severity. The final questionnaire is a follow up
questionnaire. This questionnaire also plots the degree of symptoms based on visual analogue
scores. However, subjects are further asked to rank their degree of improvement based on
percent improvement. In these last two questionnaires, subjects are asked to consider their
answers as a summary of the preceding 7 days.
Pregnancy Testing:
In all human studies, pregnancy testing will be performed 1 week prior to initiating study.
The test will specifically be performed in women of childbearing years. This will involve a
blood draw for the quantitative determination of Beta HCG. The testing is an immunoassay for
determination of total Beta HCG (Abbott Axsym Test) and performed by Cedars-Sinai Clinical
Laboratory (Los Angeles, California).
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Subjects will be selected for all studies based on the Rome I criteria. This will be
the preferred method of identifying IBS patients to avoid pre-selecting patients with
C- IBS. The goal is to evaluate methane as the determinant of transit, not
constipation or diarrhea symptoms as through Rome II criteria. All subjects who are
receiving a prokinetic drug at the time of enrollment will need to have a washout
period of 7 days before starting the study protocol. Subjects will be identified
through advertising in printed media and through the clinical operations of the GI
motility program at Cedars-Sinai Medical Center.
Exclusion Criteria:
- Subjects with a history of inflammatory bowel disease, diabetes, previous intestinal
surgery, cirrhosis, celiac disease, probiotic use, current proton pump inhibitor use,
recent antibiotic use (past 3 months), history of bowel obstruction, narcotic use or
age greater than 65 years will be excluded. Most of these conditions are known to
influence enteric bacteria levels. Women of childbearing years will undergo pregnancy
testing before participating in the study (See below for details on the pregnancy
test used). Women with positive pregnancy tests will be excluded.
Locations and Contacts
Additional Information
Starting date: July 2003
Last updated: March 17, 2008
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