Antibiotics for the Treatment of Ulcerative Colitis

February 10, 2009 updated by: University of Dundee

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Angus
      • Dundee, Angus, United Kingdom, DD1 9SY
        • Ninewells Hospital and Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
sigmoidoscopy score 0,1 and 7 months

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Dundee

Collaborators

Tenovus Scotland

Investigators

  • Principal Investigator: George T Macfarlane, BSCc, PHD, University of Dundee
  • Principal Investigator: John H Cummings, MBChB MSc MA, University of Dundee
  • Principal Investigator: Sandra Macfarlane, BSc, PhD, University of Dundee

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

July 21, 2006

First Submitted That Met QC Criteria

July 21, 2006

First Posted (Estimate)

July 24, 2006

Study Record Updates

Last Update Posted (Estimate)

February 11, 2009

Last Update Submitted That Met QC Criteria

February 10, 2009

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Tenovus 134/03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Colitis, Ulcerative

Clinical Trials on Clarithromycin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burkina Faso

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe