Study of Antibiotics in the Treatment of Colonic Crohn's Disease
Information source: Mount Sinai Hospital, Canada
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Crohn's Disease
Intervention: Metronidazole placebo (Drug); ciprofloxacin placebo (Drug); ciprofloxacin (Drug); metronidazole (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: Mount Sinai Hospital, Canada Official(s) and/or principal investigator(s): A. Hillary Steinhart, M.D., Principal Investigator, Affiliation: Mount Sinai Hospital, New York
Summary
Crohn's disease (CD) is a form of inflammatory bowel disease that can affect any part of the
digestive system. Symptoms of this chronic illness include abdominal pain, bloating,
nausea, vomiting, and diarrhea. CD also causes bowel wall ulcers, strictures (narrowings of
a hollow structure due to scar tissue and swelling), and fistulae (abnormal passages from
the intestines to another organ or to the skin).
CD is thought to arise from a combination of inherited (genetic) factors and some undefined
environmental factor(s). One environmental factor that has been shown to be intimately
involved with the development of CD is the presence of bacteria that normally inhabit the
intestines. As a result, some physicians have tried to alter the normal bacterial
population as a means of controlling the inflammation (swelling) in the intestines of
individuals with CD. Among such strategies is the use of a combination of metronidazole and
ciprofloxacin. These broad-spectrum antibiotics control CD symptoms by acting on the
intestinal bacteria that can contribute to chronic inflammation. More investigation is
needed to firmly establish the usefulness of this therapy because previous clinical trials
have given mixed results, although they have suggested that antibiotics can be particularly
useful in cases of Crohn's colitis (CD that primarily affects the large intestine). Because
these earlier studies have lacked a large enough patient population with colonic
involvement, a trial focusing on this CD subgroup with a sufficient number of subjects will
help to clarify the value of combining metronidazole and ciprofloxacin.
The proposed study will test the hypothesis that combination antibiotic therapy is effective
in the treatment of CD involving the colon. The study will compare the use of combination
therapy consisting of metronidazole and ciprofloxacin with placebo (dummy tablets) and will
examine the results of treatment at the end of 8 weeks of treatment.
Clinical Details
Official title: Metronidazole and Ciprofloxacin in the Treatment of Colonic Crohn's Disease: The MACINTOCC Trial.
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Complete response to therapy defined as a reduction of the CDAI score to below 150 points with a reduction of at least 70 points from baseline.
Secondary outcome: Partial response (improvement) will be analyzed as a secondary outcome measure and will be defined as a reduction of the CDAI score by 70 points or more but with a final value of 150 points or greater.
Detailed description:
The role of bacteria and microbial agents in the pathogenesis of Crohn's disease has been
suggested and is supported by animal models of inflammatory bowel disease (IBD) in which the
presence of normal gut flora is required for the initiation and full expression of the
inflammatory reaction. In human Crohn's disease, antibiotics are commonly used even though
the evidence to support this practice is not strong. Several studies have indicated that
antibiotics have some biological activity in Crohn's disease and that this activity may be
most pronounced in the subset of patients with colonic involvement.
In order to better justify the use of antibiotics in the treatment of Crohn's disease, the
Antibiotics for Colonic Crohn's Disease trial has been designed to determine if
ciprofloxacin and metronidazole combination therapy is effective in the treatment of active
Crohn's disease of the colon. This two arm, multi-centre, randomized, double-blind,
parallel-group, placebo-controlled study will involve 136 patients with mild to moderate
active Crohn's disease of the colon (with or without ileal involvement), as defined by a
Crohn's Disease Activity Index (CDAI) score between 220 and 450.
Eligible patients will be randomly assigned to receive one of two treatment regimens: (1)
ciprofloxacin (500 mg po bid; provided as
1 x 500 mg tablets) and metronidazole (<50 kg, 250 mg po bid; 50-75 kg, 250 mg po tid; >75
kg, 500 mg po bid; all doses provided as 1 x 250 mg tablets) or (2) placebo. Treatment will
be continued for a period of 8 weeks.
Treatment success will be defined as a complete response to therapy at the end of eight
weeks. Complete response (remission) will be defined as a reduction of the CDAI score to
below 150 points with a reduction of at least 70 points from baseline. Partial response
(improvement) will be analyzed as a secondary outcome measure and will be defined as a
reduction of the CDAI score by 70 points or more but with a final value of 150 points or
greater. Patients who experience a persistent rise in their CDAI scores of 100 points or
more on two consecutive visits or a rise in their CDAI score to 400 points or more at any
visit will be considered to be treatment failures and will be withdrawn from the study.
The primary analysis will be an intent-to-treat comparison of the proportion of patients
achieving remission by 8 weeks in the ciprofloxacin/metronidazole and placebo groups.
Secondary outcome measures will evaluate partial response and adverse event rates.
Eligibility
Minimum age: 16 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients who are 16 years of age or older.
- Patients who have been diagnosed with Crohn's disease for more than 1 month.
- Patients with CDAI scores between 220 and 450 at the randomization visit.
- Patients with Crohn's disease involving any portion of the colon (more than erythema
and/or 10 aphthoid ulcers) with or without distal or terminal ileal disease.
(Subjects may have had previous partial colonic resection consisting of less than 50%
of the estimated length of the colon.)
Exclusion Criteria:
- Female patients who are, or may become, pregnant during the course of the study or
women who are breastfeeding.
- Patients who have an allergy or contraindication to ciprofloxacin or to
metronidazole.
- Patients who are experiencing a complication of Crohn's disease (e. g. perforation,
acute obstruction, hemorrhage) requiring urgent surgical intervention.
- Patients with subacute small bowel obstruction.
- Patients with significant, symptomatic Crohn's disease of the esophagus, the stomach,
the duodenum, or the jejunum.
- Patients who have received, i)any antibiotic within 2 weeks of the screening visit,
ii)systemic corticosteroid therapy within 2 weeks of the screening visit,
iii)parenteral nutritional therapy within 2 weeks of the screening visit, iv)enteral
elemental or polymeric nutritional therapy or exclusively liquid diet within 2 weeks
of the screening visit, v) infliximab within 12 weeks of the screening visit, vi)an
initiation of therapy with sulphasalazine or with any 5-ASA preparation within 4
weeks of the screening visit or a change in the dose within 2 weeks of the screening
visit (Patients on stable doses of sulphasalazine or of a 5-ASA preparation for at
least 2 weeks prior to the screening visit are eligible for entry into the study if
the total duration of the therapy is at least 4 weeks prior to screening.), vii)an
initiation of azathioprine, 6-MP, or methotrexate within 12 weeks of the screening
visit or changes in the dose of azathioprine, of 6-MP, or of methotrexate within 4
weeks of screening visit (Patients receiving azathioprine, 6-MP, or methotrexate for
at least 12 weeks and at a stable dose for at least 4 weeks prior to the screening
visit are eligible for inclusion.), viii)other therapy not listed above for Crohn's
disease within 4 weeks of the screening visit, AND/OR ix)any investigational drug
within 12 weeks of the screening visit.
- Patients whose stool culture tests positive for enteric pathogens at the screening
visit.
- Patients whose stool assay is positive for Clostridium difficile toxin at the
screening visit.
- Patients who have another clinically significant medical or psychiatric illness (as
judged by the investigator).
- Patients who have had a resection of more than 100 cm of their small intestine, more
than half of their colon, or who have an ileostomy.
- Patients who are unable to provide informed consent.
Locations and Contacts
Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
Additional Information
Mount Sinai Hospital IBD Centre Homepage Crohn's and Colitis Foundation of Canada Homepage
Starting date: May 2006
Last updated: August 11, 2008
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