Crohn's DiseasePhase 2NCT00257699
Study of Antibiotics in the Treatment of Colonic Crohn's Disease
A Phase 2 study testing ciprofloxacin and metronidazole in people with Crohn's Disease, run by Mount Sinai Hospital, Canada at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- ciprofloxacin and metronidazole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- May 2006to Jul 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.)
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metronidazole and Ciprofloxacin in the Treatment of Colonic Crohn's Disease: The MACINTOCC Trial.
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.
Read the 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.
- Conditions
- Crohn's Disease
- Being tested
- Metronidazole placebo, ciprofloxacin placebo, ciprofloxacin, metronidazole
- Keywords
- Crohn's Disease, Randomized, Ciprofloxacin, Metronidazole, Antibiotic
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metronidazole placeboDrug
ciprofloxacin placeboDrug
ciprofloxacinDrug
Also called Cipro
500 mg bid po
metronidazoleDrug
Also called Flagyl
250 mg bid po / 250 mg tid po / 500 mg bid po depending on body weight
| Study group | Role | What they receive |
|---|---|---|
| I | Placebo comparator | Ciprofloxacin placebo and Metronidazole placebo Receives: Drug: Metronidazole placebo; Drug: ciprofloxacin placebo |
| II | Experimental | Ciprofloxacin 500 mg bid po Metronidazole - total daily dose dependent on body weight Receives: Drug: ciprofloxacin; Drug: metronidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks
Secondary outcomes (1)
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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2005 (estimated)
- Study startMay 2006
- Primary completionJul 2008
- Study completionJul 2008
Why it stopped: Inadequate recruitment to meet completion date
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Crohn's and Colitis Foundation
- Investigators
- A. Hillary Steinhart, M.D., Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00257699
- Sponsor's protocol ID
- MSH REB 04-0257-A
- Status last verified
- Aug 2008
- First submitted
- 22 Nov 2005
- Last updated
- 12 Aug 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metronidazole and Ciprofloxacin in the Treatment of Colonic Crohn's Disease: The MACINTOCC Trial.
- ClinicalTrials.gov ID
- NCT00257699
- Acronym / sponsor ID
- MSH REB 04-0257-A
- Conditions
- Crohn's Disease
- Keywords
- Crohn's Disease, Randomized, Ciprofloxacin, Metronidazole, Antibiotic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate recruitment to meet completion date
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- Crohn's and Colitis Foundation
- Study start
- May 2006
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 23 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| I | Placebo comparator | Drug: Metronidazole placebo, Drug: ciprofloxacin placeboCiprofloxacin placebo and Metronidazole placebo |
| II | Experimental | Drug: ciprofloxacin, Drug: metronidazoleCiprofloxacin 500 mg bid po Metronidazole - total daily dose dependent on body weight |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.)
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metronidazole placebo | Drug | I |
| ciprofloxacin placebo | Drug | I |
| ciprofloxacinAlso: Cipro500 mg bid po | Drug | II |
| metronidazoleAlso: Flagyl250 mg bid po / 250 mg tid po / 500 mg bid po depending on body weight | Drug | II |
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.
Time frame: 8 weeks
1 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.
Time frame: 8 weeks
Results and safety
The study was stopped early (reason given: Inadequate recruitment to meet completion date). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A. Hillary Steinhart, M.D. principal investigator
MOUNT SINAI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ciprofloxacin and metronidazole in people with Crohn's Disease, run by Mount Sinai Hospital, Canada at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Aug 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Inadequate recruitment to meet completion date). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2008.