Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Antibiotics for the Treatment of Ulcerative Colitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00355602
Recruitment Status : Completed
First Posted : July 24, 2006
Last Update Posted : February 11, 2009
Sponsor:
Collaborator:
Tenovus Scotland
Information provided by:
University of Dundee

Brief 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.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: Cefuroxime Drug: Ciprofloxacin Drug: Clarithromycin Drug: Cotrimoxazole Drug: Coamoxiclav Drug: metronidazole Drug: neomycin Drug: rifaximin Drug: Vancomycin Drug: Doxycycline Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Use of Antibiotics to Eradicate Bacterial Pathogens Colonising the Colonic Mucosa in Ulcerative Colitis Patients
Study Start Date : July 2006
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. sigmoidoscopy score 0,1 and 7 months

Secondary Outcome Measures :
  1. mucosal immune markers: human beta defensins, proinflammatory cytokines
  2. haemtaology indices
  3. biochemical indices
  4. clinical activity index
  5. bowel habit diary
  6. all at 0, 1 and 7 months


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00355602


Locations
Layout table for location information
United Kingdom
Ninewells Hospital and Medical School
Dundee, Angus, United Kingdom, DD1 9SY
Sponsors and Collaborators
University of Dundee
Tenovus Scotland
Investigators
Layout table for investigator information
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:
Layout table for additonal information
ClinicalTrials.gov Identifier: NCT00355602    
Other Study ID Numbers: Tenovus 134/03
First Posted: July 24, 2006    Key Record Dates
Last Update Posted: February 11, 2009
Last Verified: February 2009
Keywords provided by University of Dundee:
Antibiotics
Controlled Clinical Trial
Additional relevant MeSH terms:
Layout table for MeSH terms
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Metronidazole
Vancomycin
Clarithromycin
Doxycycline
Ciprofloxacin
Rifaximin
Cefuroxime
Neomycin
Trimethoprim, Sulfamethoxazole Drug Combination
Amoxicillin-Potassium Clavulanate Combination
Anti-Infective Agents
Anti-Bacterial Agents
Antiprotozoal Agents
Antiparasitic Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antimalarials