Colitis, UlcerativeNCT00355602
Antibiotics for the Treatment of Ulcerative Colitis
A study testing Cefuroxime, Ciprofloxacin and Clarithromycin in people with Colitis, Ulcerative, run by University of Dundee at 1 site in United Kingdom.
Trial summary
Ulcerative colitis (UC) is an acute and chronic inflammatory bowel disease, whose cause is unknown. However, it is widely accepted that bacteria living in the large bowel are essential for the development of the disease. Intuitively, therefore, a logical approach to treatment would be to use antibiotics. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- Cefuroxime, Ciprofloxacin and Clarithromycin
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2006to Dec 2008
- Phase
- Interventional
- 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 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Active ulcerative colitis, CAI greater than or equal to 4
Who cannot join
- Antibiotics in the last 3 months
- Probiotics
- Alteration to medications in last 3 months
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Ninewells Hospital and Medical School
Dundee, Angus, DD1 9SY
About this study
Official title: Use of Antibiotics to Eradicate Bacterial Pathogens Colonising the Colonic Mucosa in Ulcerative Colitis Patients
Ulcerative colitis (UC) is an acute and chronic inflammatory bowel disease, whose cause is unknown. However, it is widely accepted that bacteria living in the large bowel are essential for the development of the disease. Intuitively, therefore, a logical approach to treatment would be to use antibiotics. However, antimicrobial chemotherapy has been unsuccessful in managing acute colitis, and has had only limited benefit in long-term treatment. The failure of antibiotics in UC arises from the fact that no-one has tried to identify which bacteria are involved in causing disease, and equally importantly, nobody has targeted appropriate antibiotics to knock out the specific bacteria in question, in a systematic way. Despite this, increasing evidence implicates bacteria living on the lining of the bowel being involved in UC. Our aim, therefore is to identify bacteria colonizing the mucosal surface in the lower large intestine and to determine the antibiotic sensitivities of those the investigators believe to be particularly involved in the disease, such as enterococcit, peptostreptococci and enterobacteria. Because the investigators have already studied resistance to antimicrobial in many mucosal isolate, the investigators plan ot focus on using a combination of two antibiotics in this work. A controlled trial will test the benefit of using these antibiotics over a period of one month and then the patients will be followed up over a six month period. The investigators will be looking for significant long-term improvements, and a reduction in drug use following antibiotic therapy.
Read the detailed description
It is now widely acknowledged, as a result of experimental studies over the last 30 years, that the mucosal flora of the large bowel are essential to the pathogenesis of ulcerative colitis. Whilst treatment with antibiotics, therefore, might seem a logical approach, a number of clinical trials have proved disappointing. This is because the principal bacteria involved in the inflammatory process have not been identified and their sensitivities to the antibacterials determined. Moreover, we are only now beginning to understand the physiology of biofilm populations on mucosal surfaces, one property of which is antibiotic resistance. Our own studies have show a distinctive bacterial population of the mucosa with UC patients with reduced numbers of protective bifidobacteria and increased enterobacteria which we have linked to disease activity. Antibiotic resistance to commonly used gut antibiotics is widespread in these bacteria.
Our study, therefore, will commence with multiple biopsies of the distal large bowel mucosa being taken in patients with active UC and detailed microbiological characterization of the flora using viable counting, chemotaxonomy and molecular approaches. Antibiotic sensitivities of the likely pathogens will be determined and dissemination of antibiotic resistance genes in the mucosal microbiota followed using real time PCR. Markers of mucosal immune response including proinflammatory cytokines and human betea defensins will also be measured. Two weeks after initial biopsies, the patient will return to pur research IBD clinic where the appropriate combination of antibiotics will be prescribed and these will be taken for one month. A further assessment will occur at the end of this period including mucosal biopsies. endpoints will include clinical activity index, bowel habit diaries, sigmoidoscopy score, mucosal immune markers and routine haematology and biochemical indices. Because of the long term effect of antibiotics on the gut mucosa, which can last for many months, the study cannot be randomised and therefore, the run in period will be taken as a control period and the four weeks on the antibiotic will follow in all patients. The prime endpoint will be sigmoidoscopy score and the subjects will be followed up for a further six months after the study to look for long term benefits.
- Conditions
- Colitis, Ulcerative
- Being tested
- Cefuroxime, Ciprofloxacin, Clarithromycin, Cotrimoxazole, Coamoxiclav
- Keywords
- Antibiotics, Controlled Clinical Trial
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CefuroximeDrug
CiprofloxacinDrug
ClarithromycinDrug
CotrimoxazoleDrug
CoamoxiclavDrug
metronidazoleDrug
neomycinDrug
rifaximinDrug
VancomycinDrug
DoxycyclineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
sigmoidoscopy score 0,1 and 7 months
Secondary outcomes (6)
mucosal immune markers: human beta defensins, proinflammatory cytokines
haemtaology indices
biochemical indices
clinical activity index
bowel habit diary
all at 0, 1 and 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2006 (estimated)
- Study startJul 2006
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Colitis, UlcerativeStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- Tenovus Scotland
- Investigators
- George T Macfarlane, BSCc, PHD, Principal investigator, University of DundeeJohn H Cummings, MBChB MSc MA, Principal investigator, University of DundeeSandra Macfarlane, BSc, PhD, Principal investigator, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00355602
- Sponsor's protocol ID
- Tenovus 134/03
- Status last verified
- Feb 2009
- First submitted
- 21 Jul 2006
- Last updated
- 11 Feb 2009
- Results posted
- No
Publications
Montgomery SM, Morris DL, Thompson NP, Subhani J, Pounder RE, Wakefield AJ. Prevalence of inflammatory bowel disease in British 26 year olds: national longitudinal birth cohort. BMJ. 1998 Apr 4;316(7137):1058-9. doi: 10.1136/bmj.316.7137.1058. No abstract available.
PubMed 9552907Mayberry JF, Ballantyne KC, Hardcastle JD, Mangham C, Pye G. Epidemiological study of asymptomatic inflammatory bowel disease: the identification of cases during a screening programme for colorectal cancer. Gut. 1989 Apr;30(4):481-3. doi: 10.1136/gut.30.4.481.
PubMed 2785474Loftus EV Jr, Silverstein MD, Sandborn WJ, Tremaine WJ, Harmsen WS, Zinsmeister AR. Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gut. 2000 Mar;46(3):336-43. doi: 10.1136/gut.46.3.336.
PubMed 10673294Cummings JH, Macfarlane GT, Macfarlane S. Intestinal bacteria and ulcerative colitis. Curr Issues Intest Microbiol. 2003 Mar;4(1):9-20.
PubMed 12691258Onderdonk AB, Bartlett JG. Bacteriological studies of experimental ulcerative colitis. Am J Clin Nutr. 1979 Jan;32(1):258-65. doi: 10.1093/ajcn/32.1.258. No abstract available.
PubMed 760501Macfarlane S, Furrie E, Cummings JH, Macfarlane GT. Chemotaxonomic analysis of bacterial populations colonizing the rectal mucosa in patients with ulcerative colitis. Clin Infect Dis. 2004 Jun 15;38(12):1690-9. doi: 10.1086/420823. Epub 2004 May 25.
PubMed 15227614Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O'neil DA, Macfarlane GT. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut. 2005 Feb;54(2):242-9. doi: 10.1136/gut.2004.044834.
PubMed 15647189
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Antibiotics to Eradicate Bacterial Pathogens Colonising the Colonic Mucosa in Ulcerative Colitis Patients
- ClinicalTrials.gov ID
- NCT00355602
- Acronym / sponsor ID
- Tenovus 134/03
- Conditions
- Colitis, Ulcerative
- Keywords
- Antibiotics, Controlled Clinical Trial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- Tenovus Scotland
- Study start
- Jul 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 24 Jul 2006 (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.
Ulcerative colitis (UC) is an acute and chronic inflammatory bowel disease, whose cause is unknown. However, it is widely accepted that bacteria living in the large bowel are essential for the development of the disease. Intuitively, therefore, a logical approach to treatment would be to use antibiotics. However, antimicrobial chemotherapy has been unsuccessful in managing acute colitis, and has had only limited benefit in long-term treatment. The failure of antibiotics in UC arises from the fact that no-one has tried to identify which bacteria are involved in causing disease, and equally importantly, nobody has targeted appropriate antibiotics to knock out the specific bacteria in question, in a systematic way. Despite this, increasing evidence implicates bacteria living on the lining of the bowel being involved in UC. Our aim, therefore is to identify bacteria colonizing the mucosal surface in the lower large intestine and to determine the antibiotic sensitivities of those the investigators believe to be particularly involved in the disease, such as enterococcit, peptostreptococci and enterobacteria. Because the investigators have already studied resistance to antimicrobial in many mucosal isolate, the investigators plan ot focus on using a combination of two antibiotics in this work. A controlled trial will test the benefit of using these antibiotics over a period of one month and then the patients will be followed up over a six month period. The investigators will be looking for significant long-term improvements, and a reduction in drug use following antibiotic therapy.
Detailed description
It is now widely acknowledged, as a result of experimental studies over the last 30 years, that the mucosal flora of the large bowel are essential to the pathogenesis of ulcerative colitis. Whilst treatment with antibiotics, therefore, might seem a logical approach, a number of clinical trials have proved disappointing. This is because the principal bacteria involved in the inflammatory process have not been identified and their sensitivities to the antibacterials determined. Moreover, we are only now beginning to understand the physiology of biofilm populations on mucosal surfaces, one property of which is antibiotic resistance. Our own studies have show a distinctive bacterial population of the mucosa with UC patients with reduced numbers of protective bifidobacteria and increased enterobacteria which we have linked to disease activity. Antibiotic resistance to commonly used gut antibiotics is widespread in these bacteria.
Our study, therefore, will commence with multiple biopsies of the distal large bowel mucosa being taken in patients with active UC and detailed microbiological characterization of the flora using viable counting, chemotaxonomy and molecular approaches. Antibiotic sensitivities of the likely pathogens will be determined and dissemination of antibiotic resistance genes in the mucosal microbiota followed using real time PCR. Markers of mucosal immune response including proinflammatory cytokines and human betea defensins will also be measured. Two weeks after initial biopsies, the patient will return to pur research IBD clinic where the appropriate combination of antibiotics will be prescribed and these will be taken for one month. A further assessment will occur at the end of this period including mucosal biopsies. endpoints will include clinical activity index, bowel habit diaries, sigmoidoscopy score, mucosal immune markers and routine haematology and biochemical indices. Because of the long term effect of antibiotics on the gut mucosa, which can last for many months, the study cannot be randomised and therefore, the run in period will be taken as a control period and the four weeks on the antibiotic will follow in all patients. The prime endpoint will be sigmoidoscopy score and the subjects will be followed up for a further six months after the study to look for long term benefits.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Active ulcerative colitis, CAI greater than or equal to 4
Key exclusion criteria (3 listed)
- Antibiotics in the last 3 months
- Probiotics
- Alteration to medications in last 3 months
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 |
|---|---|---|
| Cefuroxime | Drug | – |
| Ciprofloxacin | Drug | – |
| Clarithromycin | Drug | – |
| Cotrimoxazole | Drug | – |
| Coamoxiclav | Drug | – |
| metronidazole | Drug | – |
| neomycin | Drug | – |
| rifaximin | Drug | – |
| Vancomycin | Drug | – |
| Doxycycline | Drug | – |
Primary outcome
sigmoidoscopy score 0,1 and 7 months
6 secondary outcomes
mucosal immune markers: human beta defensins, proinflammatory cytokines
haemtaology indices
biochemical indices
clinical activity index
bowel habit diary
all at 0, 1 and 7 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2009.
- Background: PubMed 9552907Montgomery SM, Morris DL, Thompson NP, Subhani J, Pounder RE, Wakefield AJ. Prevalence of inflammatory bowel disease in British 26 year olds: national longitudinal birth cohort. BMJ. 1998 Apr 4;316(7137):1058-9. doi: 10.1136/bmj.316.7137.1058. No abstract available.
- Background: PubMed 2785474Mayberry JF, Ballantyne KC, Hardcastle JD, Mangham C, Pye G. Epidemiological study of asymptomatic inflammatory bowel disease: the identification of cases during a screening programme for colorectal cancer. Gut. 1989 Apr;30(4):481-3. doi: 10.1136/gut.30.4.481.
- Background: PubMed 10673294Loftus EV Jr, Silverstein MD, Sandborn WJ, Tremaine WJ, Harmsen WS, Zinsmeister AR. Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gut. 2000 Mar;46(3):336-43. doi: 10.1136/gut.46.3.336.
- Background: PubMed 12691258Cummings JH, Macfarlane GT, Macfarlane S. Intestinal bacteria and ulcerative colitis. Curr Issues Intest Microbiol. 2003 Mar;4(1):9-20.
- Background: PubMed 760501Onderdonk AB, Bartlett JG. Bacteriological studies of experimental ulcerative colitis. Am J Clin Nutr. 1979 Jan;32(1):258-65. doi: 10.1093/ajcn/32.1.258. No abstract available.
- Background: PubMed 15227614Macfarlane S, Furrie E, Cummings JH, Macfarlane GT. Chemotaxonomic analysis of bacterial populations colonizing the rectal mucosa in patients with ulcerative colitis. Clin Infect Dis. 2004 Jun 15;38(12):1690-9. doi: 10.1086/420823. Epub 2004 May 25.
- Background: PubMed 15647189Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O'neil DA, Macfarlane GT. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut. 2005 Feb;54(2):242-9. doi: 10.1136/gut.2004.044834.
Related trials for Colitis, Ulcerative
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
Ibd CAncer and seRious Infections in France (I-CARE 2)
IBD, Ulcerative Colitis
RecruitingObservational study
Characterization of Colorectal Dysplasic Lesions and Stratification of Their Evolving Risk in Inflammatory Bowel Disease Patients: a Prospective, Observational and Multicenter Study
Crohn Disease (CD), Colitis Ulcerative
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
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.
George T Macfarlane, BSCc, PHD principal investigator
University of Dundee
John H Cummings, MBChB MSc MA principal investigator
University of Dundee
Sandra Macfarlane, BSc, PhD principal investigator
University of Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cefuroxime, Ciprofloxacin and Clarithromycin in people with Colitis, Ulcerative, run by University of Dundee at 1 site in United Kingdom.
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 1 inclusion and 3 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: finished, as of the sponsor's last update on 11 Feb 2009. 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 United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
sigmoidoscopy score 0,1 and 7 months. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00355602, which also lists 7 linked publications.
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 11 Feb 2009.