Saccharomyces Cerevisiae CNCM I-3856 Treatment in Irritable Bowel Syndrome With Diarrhea (IBS-D) and Post Infective Bowel Dysfunction

This study has been withdrawn prior to enrollment.
(unable to get MHRA approval for formulation in present form)
Sponsor:
Collaborator:
Lesaffre International
Information provided by:
University of Nottingham
ClinicalTrials.gov Identifier:
NCT00977587
First received: September 15, 2009
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

Irritable Bowel Syndrome (IBS) is a common condition characterised by abdominal pain or discomfort and altered bowel habit affecting up to 10% of the population. There are several groups of patients that are based on differing bowel patterns including IBS with diarrhea (IBS-D) and those with post infective IBS (PI-IBS) whose symptoms begin after an acute infection. Saccharomyces cerevisiae, the yeast used in bread making has been shown to reduce the duration of infectious diarrhoea. Part of the benefit maybe that it can destroy bacterial toxins. Recent studies suggest an increase in proteases (chemicals which breakdown proteins) in the stool of patients with IBS-D. The investigators think that this yeast may benefit patients with IBS-D and PI-IBS by reducing the amount of protease in stool. This is important because proteases have been shown to be potentially important in generating some of the discomfort experienced by patients. The investigators will study patients with chronic IBS-D who will receive 2 weeks treatment with the yeast or placebo followed by a 4 week gap and then a further 2 week treatment with placebo or the yeast, with the treatments allocated randomly. The investigators will also study 30 subjects who still have persistent loose bowel function 6 weeks after an infection with Campylobacter jejuni, one of the commonest causes of gastroenteritis in the UK. Subjects will be randomised to take either the yeast or placebo for 4 weeks . In both studies, the investigators will examine the effect of treatment on stool proteases, stool frequency and consistency and abdominal discomfort; the investigators will also take blood samples to examine some aspects of immune system function. The results of the study may suggest how yeast provides a benefit in patients with IBS and diarrhea and will provide data for a larger clinical trial.


Condition Intervention
Irritable Bowel Syndrome
Post Infective Bowel Dysfunction
Drug: Saccharomyces Cerevisiae CNCM I-3856
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Saccharomyces Cerevisiae CNCM I-3856 on Faecal Proteases and Symptoms Associated With IBS-D and Postinfective Bowel Dysfunction

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Change in faecal serine protease activity [ Time Frame: at 4 and 9 weeks for study 1 and 10 weeks for study 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Stool consistency [ Time Frame: at 4 and 9 weeks for study 1 and ten weeks for study 2 ] [ Designated as safety issue: No ]
  • Stool frequency [ Time Frame: at 4 and 9 weeks for study 1 and 10 weeks for study 2 ] [ Designated as safety issue: No ]
  • Number of mucus septae per high power filed [ Time Frame: at 4 and 9 weeks for study 1 and 10 weeks for study 2 ] [ Designated as safety issue: No ]
  • In vitro effect of Saccharomyces cerevisiae CNCM I-3856 supernatant on IBS-D faecal proteases [ Time Frame: at week one for both studies ] [ Designated as safety issue: No ]
  • Bacterial diversity assessed by similarity indices [ Time Frame: at week 1 for both studies at week 4 and 9 for study 1 and week 10 for study 2 ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: January 2011
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Saccharomyces Cerevisiae CNCM I-3856
2 weeks of treatment with Saccharomyces Cerevisiae CNCM I-3856 1 capsule twice a day, 500 mg per capsule (5 X109 living cells). Living cells are estimated by the method of colony forming units (cfu).
Drug: Saccharomyces Cerevisiae CNCM I-3856
Saccharomyces cerevisiae CNCM I-3856, 500 mg per capsule (5 X109 living cells). Living cells are estimated by the method of colony forming units (cfu).subjects will take 1 capsule twice a day
Placebo Comparator: placebo

Capsules will contain 500 mg of the following formulation and will not contain Saccharomyces cerevisiae CNCM I-3856:

  • Calcium phosphate, Dibasic 472.0 mg
  • Maltodextrin DE14 112.1 mg
  • Vegetal magnesium stearate 5.9 mg subjects will take one capsule twice a day
Drug: placebo

Placebo: Capsules will contain 500 mg of the following formulation and will not contain Saccharomyces cerevisiae CNCM I-3856:

  • Calcium phosphate, Dibasic 472.0 mg
  • Maltodextrin DE14 112.1 mg
  • Vegetal magnesium stearate 5.9 mg subjects will take one capsule twice a day

Detailed Description:

The participant involvement in study 1 & 2 will last 15 & 9 weeks respectively. Study1 has a cross over design so each participant will receive two 2 week treatment periods (1 of placebo and 1 of active) with a 4 week washout period in between. The order with which they receive the treatment will be decided randomly. The study starts with a screening period lasting 1 week. If, at the end of screening, they are still eligible they will be enrolled and start randomised treatment. Once the participant has received both treatments the study finishes.

Study 2 is a parallel group design. Subjects who submit a stool sample which proves to be positive for Campylobacter will be sent an invitation to take part. All subjects will be asked to complete a bowel symptom questionnaire and attend to provide a stool sample (enrolment visit). A blood sample will be taken at this visit.

After a further 4 weeks subjects will attend again, bringing with them a stool sample and stool symptom diaries. A blood sample will be taken. At this time, if they are still symptomatic they will be invited to take part in the randomised placebo controlled trial taking yeast or placebo for 5 weeks, after which they will again attend with stool diaries and provide a final stool and blood sample. The blood sample will be used to see, if antibodies to C. jejuni antigens predicts recovery and whether this is altered by yeast treatment. Those that are asymptomatic will not take part in the RCT but will return at 9 weeks with a further stool and blood sample.

We will also invite 15 healthy volunteers, free from gastrointestinal complaints to attend on 3 occasions mimicking visits 1-3 by providing stool and blood samples so we can define the normal variability in stool composition in health. As with the other subjects they will be required to avoid antibiotics and probiotics during the study.

End of Studies The last visit of the last subject.

SELECTION AND WITHDRAWAL OF PARTICIPANTS Recruitment Study 1 Participants for study 1 will be recruited from Professor Spiller's patients who have previously taken part in research studies and have indicated that they would like to be contacted about future relevant research projects. This secure password protected database is held within the Nottingham Digestive Diseases Centre and contains patient's names and addresses to allow mailing of invitation letter.

The investigator or their nominee, i.e. a member of the participant's usual care team, will make the initial approach to the patient by letter to the patient using a ethically approved invitation letter enclosing a copy of the information sheet and inform the participant of all aspects pertaining to participation in the study.

Study 2 Currently all patients who submit a stool sample positive for C jejuni to the Public Health laboratory receive a letter form Professor Neal asking for details about eating out and pet's illnesses as part of routine surveillance. This letter will have an information sheet enclosed and an invitation to take part in Study 2 We will also recruit 15 healthy volunteers who have responded to an advert displayed on public notice boards at University Hospital Nottingham. On responding, they will then be sent an information sheet and details of the study and who to contact if they are interested in taking part.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Study 1 and 2:

  • Male or female aged 18-75 years
  • Subjects who are able to give informed consent

Study 1:

  • IBS-D patients meeting Rome III Criteria

Study 2:

  • Subjects with stool cultures positive for Campylobacter jejuni
  • Healthy volunteer controls

Exclusion Criteria:

  • Subjects that, in the opinion of the investigator, are considered unsuitable.
  • Subjects who have had abdominal surgery which may cause bowel symptoms similar to IBS (Please note, appendicectomy and cholecystectomy is not an exclusion).
  • Subjects with a known intolerance to yeast.
  • Subjects taking immunosuppressant medication, e.g. long term steroids, or who might otherwise be immunocompromised.
  • Subjects who have had a recent course of antibiotics (in the last 28 days).
  • Subjects unable to stop anti-diarrhoeal drugs.
  • Subjects currently participating in another clinical trial or who have been in a trial in the previous three months.
  • Patients with known gastrointestinal diseases including coeliac disease and inflammatory bowel disease.
  • Regular consumption of drugs known to alter bowel habit (see concomitant medication).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00977587

Locations
United Kingdom
Nottingham University Hospital
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
Lesaffre International
Investigators
Principal Investigator: Robin Spiller, MB B Chir Cantab, MSc Lond, MD Nottingham Digestive Diseases Centre and Biomedical Research Unit
  More Information

No publications provided

Responsible Party: Professor Robin Spiller, Nottingham dDigestive Diseases Biomedical Research Unit
ClinicalTrials.gov Identifier: NCT00977587     History of Changes
Other Study ID Numbers: 09075
Study First Received: September 15, 2009
Last Updated: January 18, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Nottingham:
irritable bowel syndrome
faecal serine proteases

Additional relevant MeSH terms:
Gastrointestinal Diseases
Intestinal Diseases
Irritable Bowel Syndrome
Syndrome
Colonic Diseases
Colonic Diseases, Functional
Digestive System Diseases
Disease
Pathologic Processes

ClinicalTrials.gov processed this record on October 23, 2014