Antibiotics for the Treatment of Ulcerative Colitis

Colitis, Ulcerative Clinical Trial

Official title:

Use of Antibiotics to Eradicate Bacterial Pathogens Colonising the Colonic Mucosa in Ulcerative Colitis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00355602
• Other study ID #: Tenovus 134/03
• Status: Completed
• Phase: N/A
• First received: July 21, 2006
• Last updated: February 10, 2009
• Start date: July 2006
• Est. completion date: December 2008

Study information

• Verified date: February 2009
• Source: University of Dundee
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Active ulcerative colitis, CAI greater than or equal to 4

Exclusion Criteria:

• Antibiotics in the last 3 months

• Probiotics

• Alteration to medications in last 3 months

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Cefuroxime

• Ciprofloxacin

• Clarithromycin

• Cotrimoxazole

• Coamoxiclav

• metronidazole

• neomycin

• rifaximin

• Vancomycin

• Doxycycline

Locations

Country	Name	City	State
United Kingdom	Ninewells Hospital and Medical School	Dundee	Angus

Sponsors (2)

Lead Sponsor	Collaborator
University of Dundee	Tenovus Scotland

Country where clinical trial is conducted

United Kingdom, 

References & Publications (7)

Cummings JH, Macfarlane GT, Macfarlane S. Intestinal bacteria and ulcerative colitis. Curr Issues Intest Microbiol. 2003 Mar;4(1):9-20. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Onderdonk AB, Bartlett JG. Bacteriological studies of experimental ulcerative colitis. Am J Clin Nutr. 1979 Jan;32(1):258-65. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	sigmoidoscopy score 0,1 and 7 months
Secondary	mucosal immune markers: human beta defensins, proinflammatory cytokines
Secondary	haemtaology indices
Secondary	biochemical indices
Secondary	clinical activity index
Secondary	bowel habit diary
Secondary	all at 0, 1 and 7 months