Antibiotics for the Treatment of Ulcerative Colitis
Information source: University of Dundee
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Colitis, Ulcerative
Intervention: Cefuroxime (Drug); Ciprofloxacin (Drug); Clarithromycin (Drug); Cotrimoxazole (Drug); Coamoxiclav (Drug); metronidazole (Drug); neomycin (Drug); rifaximin (Drug); Vancomycin (Drug); Doxycycline (Drug)
Sponsored by: University of Dundee
Official(s) and/or principal investigator(s):
George T Macfarlane, BSCc, PHD, Principal Investigator, Affiliation: University of Dundee
John H Cummings, MBChB MSc MA, Principal Investigator, Affiliation: University of Dundee
Sandra Macfarlane, BSc, PhD, Principal Investigator, Affiliation: University of Dundee
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
Official title: Use of Antibiotics to Eradicate Bacterial Pathogens Colonising the Colonic Mucosa in Ulcerative Colitis Patients
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: sigmoidoscopy score 0,1 and 7 months
mucosal immune markers: human beta defensins, proinflammatory cytokines
clinical activity index
bowel habit diary
all at 0, 1 and 7 months
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.
Minimum age: 18 Years.
Maximum age: 79 Years.
- Active ulcerative colitis, CAI greater than or equal to 4
- Antibiotics in the last 3 months
- Alteration to medications in last 3 months
Locations and Contacts
Ninewells Hospital and Medical School, Dundee, Angus DD1 9SY, United Kingdom
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.
Mayberry 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.
Loftus 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.
Cummings JH, Macfarlane GT, Macfarlane S. Intestinal bacteria and ulcerative colitis. Curr Issues Intest Microbiol. 2003 Mar;4(1):9-20. Review.
Onderdonk AB, Bartlett JG. Bacteriological studies of experimental ulcerative colitis. Am J Clin Nutr. 1979 Jan;32(1):258-65.
Macfarlane 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. Epub 2004 May 25.
Furrie 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.
Starting date: July 2006
Last updated: February 10, 2009