Irritable Bowel SyndromePhase 4NCT00418340
Manipulation of Visceral Sensitivity and Immune System in IBS
A Phase 4 study testing probiotic (bacterial/dietary supplement) in people with Irritable Bowel Syndrome, run by London North West Healthcare NHS Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Irritable Bowel Syndrome
- What is being tested?
- probiotic (bacterial/dietary supplement)
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2007to not given
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- patients fulfilling the Rome II criteria for the diagnosis of IBS
- normal blood investigations
- normal colonoscopy
Who cannot join
- a history of weight loss
- rectal bleeding
- fevers
- psychiatric illness (severe depression, anxiety, mania and schizophrenia)
- active infection
- recent antibiotic therapy or anti-inflammatory medication within previous 4 weeks
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
North West London Hospitals NHS Trust - St Mark's
London, Middlesex, HA1 3UJ
Alan Warnes, PhD, 020 8869 ext. 2011, alan.warnes@nwlh.nhs.uk
Iva Hauptmannova, BSc, MA, iva.hauptmannova@nwlh.nhs.uk
About this study
Official title: 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.
Read more
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.
Read the detailed description
This research will study
- 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.
- Assessing the clinical response to therapy
- Physiological response to probiotic therapy: Rectal sensitivity will be assessed at baseline and at day 28 of therapy. Rectal sensitivity to pressure and pain will be assessed with Barostat device and electrical stimulation respectively. Barostat device has been used in many other studies as a measure of sensation to pressure. Electrical stimulation is currently used in clinical practice. Equipment for both tests is currently in use at out physiology laboratory.
- Symptomatic response to probiotic therapy: IBS symptom scores will be made at baseline and at d28 of therapy. The three symptoms of IBS will be assessed to determine response to therapy: abdominal pain/discomfort, bloating/ distension and bowel movements, each scored on an ordinal scale (Likert scale; maximum score 7) and on a 100mm visual analogue scale (VAS; maximum score 100). A composite score with the sums of the 3 cardinal symptoms will also be calculated for each patient (Likert scale maximum score 21) (VAS; maximum score 300).
- Quality of life (QOL) with probiotic therapy: The SF-36 Heath-related QOL questionnaire, and the IBS QOL questionnaire will be administered at baseline and at day 28. This will assess the impact of IBS symptoms on the QOL and any changes following probiotic therapy. Follow-up: Patients will be contacted at 6 months to reassess symptom scores and QOL and determine longer-term impact of therapy.
- Assessing Immunological response to probiotic therapy. Venepuncture will be performed for collection of blood immune cells at baseline and day 28. Colonic biopsies will be collected via a flexible sigmoidoscopy at entry baseline and at day 28 following the physiological tests. The biopsies will be use for analysis of cytokine production and to a limited phenotypic analysis of colonic immune cells (DC) with markers to be selected on the basis of data from an on-going cross-sectional study looking at DC in IBS compared to controls. Full analysis of blood DC will be performed at each time point. Changes in DC populations and cytokine production will be secondary endpoints of the study.
- Conditions
- Irritable Bowel Syndrome
- Being tested
- probiotic (bacterial/dietary supplement)
- Keywords
- Irritable Bowel Syndrome,, Visceral hypersensitivity,, probiotic therapy,, immune response
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
probiotic (bacterial/dietary supplement)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure is the change in physiological rectal sensitivity and before and after probiotic
therapy.
Secondary outcomes (2)
Secondary outcome measures are the change symptoms and QOL induced by probiotic therapy and the
change in the immune response after probiotic therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2007 (estimated)
- Study startDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London North West Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Investigators
- Naila Arebi, MD, PhD, MRCP, Principal investigator, London North West Healthcare NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00418340
- Sponsor's protocol ID
- 07.IBS.1
- Status last verified
- Nov 2007
- First submitted
- 2 Jan 2007
- Last updated
- 16 Nov 2007
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00418340
- Acronym / sponsor ID
- 07.IBS.1
- Conditions
- Irritable Bowel Syndrome
- Keywords
- Irritable Bowel Syndrome,, Visceral hypersensitivity,, probiotic therapy,, immune response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- London North West Healthcare NHS TrustUniversity, hospital or other
- Study start
- Dec 2007
- First posted
- 4 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This research will study
- 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.
- Assessing the clinical response to therapy
- Physiological response to probiotic therapy: Rectal sensitivity will be assessed at baseline and at day 28 of therapy. Rectal sensitivity to pressure and pain will be assessed with Barostat device and electrical stimulation respectively. Barostat device has been used in many other studies as a measure of sensation to pressure. Electrical stimulation is currently used in clinical practice. Equipment for both tests is currently in use at out physiology laboratory.
- Symptomatic response to probiotic therapy: IBS symptom scores will be made at baseline and at d28 of therapy. The three symptoms of IBS will be assessed to determine response to therapy: abdominal pain/discomfort, bloating/ distension and bowel movements, each scored on an ordinal scale (Likert scale; maximum score 7) and on a 100mm visual analogue scale (VAS; maximum score 100). A composite score with the sums of the 3 cardinal symptoms will also be calculated for each patient (Likert scale maximum score 21) (VAS; maximum score 300).
- Quality of life (QOL) with probiotic therapy: The SF-36 Heath-related QOL questionnaire, and the IBS QOL questionnaire will be administered at baseline and at day 28. This will assess the impact of IBS symptoms on the QOL and any changes following probiotic therapy. Follow-up: Patients will be contacted at 6 months to reassess symptom scores and QOL and determine longer-term impact of therapy.
- Assessing Immunological response to probiotic therapy. Venepuncture will be performed for collection of blood immune cells at baseline and day 28. Colonic biopsies will be collected via a flexible sigmoidoscopy at entry baseline and at day 28 following the physiological tests. The biopsies will be use for analysis of cytokine production and to a limited phenotypic analysis of colonic immune cells (DC) with markers to be selected on the basis of data from an on-going cross-sectional study looking at DC in IBS compared to controls. Full analysis of blood DC will be performed at each time point. Changes in DC populations and cytokine production will be secondary endpoints of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- patients fulfilling the Rome II criteria for the diagnosis of IBS
- normal blood investigations
- normal colonoscopy
Key exclusion criteria (6 listed)
- a history of weight loss
- rectal bleeding
- fevers
- psychiatric illness (severe depression, anxiety, mania and schizophrenia)
- active infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| probiotic (bacterial/dietary supplement) | Drug | – |
Primary outcome
The primary outcome measure is the change in physiological rectal sensitivity and before and after probiotic
therapy.
2 secondary outcomes
Secondary outcome measures are the change symptoms and QOL induced by probiotic therapy and the
change in the immune response after probiotic therapy.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2007.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naila Arebi, MD, PhD, MRCP principal investigator
London North West Healthcare NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing probiotic (bacterial/dietary supplement) in people with Irritable Bowel Syndrome, run by London North West Healthcare NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Nov 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Naila Arebi, MD,PhD, MRCP (020 8235 ext. 4089, n.arebi@doctors.org.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome measure is the change in physiological rectal sensitivity and before and after probiotic. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2007.