Manipulation of Visceral Sensitivity and Immune System in IBS
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|ClinicalTrials.gov Identifier: NCT00418340|
Recruitment Status : Unknown
Verified November 2007 by London North West Healthcare NHS Trust.
Recruitment status was: Not yet recruiting
First Posted : January 4, 2007
Last Update Posted : November 16, 2007
|First Submitted Date ICMJE||January 2, 2007|
|First Posted Date ICMJE||January 4, 2007|
|Last Update Posted Date||November 16, 2007|
|Study Start Date ICMJE||December 2007|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00418340 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Manipulation of Visceral Sensitivity and Immune System in IBS|
|Official Title ICMJE||Bacteria and Cytokines as Factors Modulating Visceral Afferent Processing in Irritable Bowel Syndrome: Manipulation of Intestinal Bacteria and Mucosal Cytokines by Probiotic Therapy and the Effect on Visceral Hypersensitivity|
Irritable bowel syndrome (IBS) is a common condition. At least 20% of the population suffer from IBS. The symptoms of abdominal pain, diarrhoea, constipation, bloating and difficulty with bowel motions are often disabling. Many of those affected are young and report a poor quality of life (QOL) to a degree that is similar to gut inflammatory conditions like ulcerative colitis and Crohn's disease. Yet the impact of IBS on patients' lives is often underestimated. This is probably because unlike inflammatory bowel disease, in which the bowel is inflammed and bleeds, the bowel in IBS looks normal. Instead the problem is of abnormal functioning of the gut the cause of which is unknown.
Currently therapy for IBS is limited and until recently therapy has focused on treating the symptoms to improve QOL primarily because the underlying mechanism of IBS is poorly understood. However as more processes are being implicated in IBS e.g. visceral hypersensitivity (excessive response to sensory stimuli within the gut), infection, immune activation, dysmotility and abnormal gut fermentation , the potential for new therapies looks promising. The evidence that gut bacteria play a role in inducing IBS symptoms is due to observations of an improvement of IBS symptoms with probiotic therapy (bacterial supplements) and antibiotic therapy.
Patients with IBS are hypersensitive to colorectal distension compared with healthy controls. Studies carried out in our unit have shown that visceral pain thresholds in response to stress are lower in patients with IBS compared with healthy volunteers. This hypersensitivity is apparent in response to both a physical and chemical stimulus but the triggers to visceral hypersensitivity remain largely unknown. Animal models suggest roles for both host immune response and intestinal bacteria in the induction of visceral hypersensitivity. This proposal will focus on further exploration of the mechanisms underlying visceral hypersensitivity to direct future targeting of therapy.
Previous independent studies showed that (a) bacteria reduce visceral hypersensitivity, (b)probiotic therapy can alter gut immune response and (c) gut sensation is affected by the type of immune cells in the gut. Our research proposal will investigate the relationship between gut bacteria, the immune system and the sensory gut nerves in order to understand how IBS symptoms are generated. This understanding will be the critical for effective future drug treatment.
This research will study
1) probiotic−induced changes in visceral hypersensitivity and immune activity The effects of probiotic therapy will be assessed in a randomised placebo−controlled study. Subjects will be recruited prospectively from outpatient clinics. A flow chart of the study is shown in appendix 1 of the protocol. Patient selection. IBS patients will be selected according to inclusion and exclusion criteria.
Disease severity will be determined at enrolment with a validated IBS symptom questionnaire.
Questionnaires to exclude psychiatric illness: The well−validated Hospital Anxiety Depression Score (HADS)questionniaire will be used to identify patients with anxiety and depression. A SCL−90 questionnaire will also be used to assess the psychological profile of patients as this may have an impact on the response to therapy.
Probiotic therapy. Patients will be randomised to receive either VSL#3 (450 billion lyophilized bacteria/sachet) twice daily for 4 weeks or a placebo powder containing starch but no bacteria. VSL#3 was selected for use in this study because (a) it contains three different Bifidobacteria strains (in addition to lactobaccilli and streptococci) and the limited evidence available Bifidobacteria as the most effective probiotics in IBS 10; (b)it induces IL−10 production by intestinal DC 27 and, in pouchitis studies, stimulated IL−10 production in vivo 38; IBS has been associated with a deficiency in IL−10 production; (c) studies from one group have yielded promising results with this particular probiotic preparation.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Irritable Bowel Syndrome|
|Intervention ICMJE||Drug: probiotic (bacterial/dietary supplement)|
|Study Arms||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE
|Original Enrollment ICMJE||Same as current|
|Study Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United Kingdom|
|Removed Location Countries|
|NCT Number ICMJE||NCT00418340|
|Other Study ID Numbers ICMJE||07.IBS.1|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||London North West Healthcare NHS Trust|
|Collaborators ICMJE||Not Provided|
|PRS Account||London North West Healthcare NHS Trust|
|Verification Date||November 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP