The Effect of VSL#3 Probiotic Preparation on the Bile Acid Metabolism in Patients With Inflammatory Bowel Disease

This study is currently recruiting participants.
Verified March 2014 by Charles University, Czech Republic
Sponsor:
Collaborators:
Iscare i.v.f., Czech Republic
CD Investments srl
University Of Perugia
University of Roma La Sapienza
Information provided by (Responsible Party):
Martin Lenicek, Charles University, Czech Republic
ClinicalTrials.gov Identifier:
NCT01765439
First received: January 7, 2013
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

The aim of the study is to determine, whether administration of VSL#3 probiotic preparation can alter the bile acid metabolism in patients with inflammatory bowel disease.


Condition Intervention
Crohn Disease
Ulcerative Colitis
Dietary Supplement: VSL#3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Effect of VSL#3 Probiotic Preparation on the Bile Acid Metabolism in Patients With Inflammatory Bowel Disease

Resource links provided by NLM:


Further study details as provided by Charles University, Czech Republic:

Primary Outcome Measures:
  • Alteration in the rate of bile acid synthesis [ Time Frame: Baseline and 6 weeks (plus or minus 5 days) ] [ Designated as safety issue: No ]
    Will be assessed as difference between serum levels of fibroblast growth factor 19 and C4 at baseline and 6 weeks, respectively.


Secondary Outcome Measures:
  • Change of the spectrum of bile acids in stools and plasma [ Time Frame: Baseline and 6 weeks (plus or minus 5 days). ] [ Designated as safety issue: No ]
  • Change of a metabolomic profile in urine [ Time Frame: Baseline and 6 weeks (plus or minus 5 days). ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change of the disease activity [ Time Frame: Baseline and 6 weeks (plus or minus 5 days). ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: February 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CD resected
Patients with Crohn´s disease with the history of single resection (<60 cm) of distal leum.
Dietary Supplement: VSL#3
Study subjects will receive two sachets of VSL#3 probiotic (ie 2x900 billions of live bacteria) per day (one in the morning, one in the evening). The intervention period will be 6 weeks (plus or minus 5 days).
Experimental: UC unoperated
Patients with ulcerative colitis without history of gut resection.
Dietary Supplement: VSL#3
Study subjects will receive two sachets of VSL#3 probiotic (ie 2x900 billions of live bacteria) per day (one in the morning, one in the evening). The intervention period will be 6 weeks (plus or minus 5 days).
Experimental: UC IPAA
Patients with ulcerative colitis after proctocolectomy and ileal pouch-anal anastomosis(IPAA).
Dietary Supplement: VSL#3
Study subjects will receive two sachets of VSL#3 probiotic (ie 2x900 billions of live bacteria) per day (one in the morning, one in the evening). The intervention period will be 6 weeks (plus or minus 5 days).
Experimental: Healthy volunteers
Subjects without any sign of disease of the digestive tract.
Dietary Supplement: VSL#3
Study subjects will receive two sachets of VSL#3 probiotic (ie 2x900 billions of live bacteria) per day (one in the morning, one in the evening). The intervention period will be 6 weeks (plus or minus 5 days).

Detailed Description:

VSL#3, a potent probiotic preparation, has been tested as an adjuvant therapy in inflammatory bowel diseases (IBD), chronic unspecific inflammatory disorders of the gastrointestinal tract (the most frequent forms of IBD are Crohn's disease (CD) and ulcerative colitis (UC)). VSL#3 has been shown to improve symptoms of IBD both in animal models and in humans-the most impressive results have been observed in preventing of pouchitis in UC patients. Several possible mechanisms of its action have been suggested, including change in gut microbial diversity, immunomodulatory function (upregulation of interleukine-10), etc., however, the list is probably far from complete.

Bile acids (BA) play an important role in the gastrointestinal tract - besides facilitating fat (and protein) digestion and resorption, they act as general antimicrobial agents within the small intestine (maintaining the small intestine more or less microbe-free), colonic microflora modifiers, intestinal innate immunity regulators, and importantly as signalling molecules on the liver-intestine/intestine-liver axis. Under pathological conditions (such as BA malabsorption) BA can worsen the IBD symptoms (namely diarrhoea), by irritating colonic mucosa or by inducing colonic secretion of electrolytes.

The study hypothesis is that the beneficial effect of VSL#3 might be partially explained by alteration of BA metabolism. There exists a complex crosstalk between gut microflora and BA: BA affect microbial growth, whereas BA structure is modified by bacteria (deconjugation, 7 α dehydroxylation). Several observations might support this hypothesis: VSL#3 ameliorates symptoms of radiation or chemotherapy induced diarrhoea, as well as diarrhoea of critically ill patients - conditions, that can be caused by BA malabsorption. Similarly, oxalate absorption (closely related to BA malabsorption) has been shown to be lowered by VSL#3. The main question to be addressed in the proposed study is, therefore, whether VSL#3 administration can somehow change metabolism of bile acids (BA).

Additionally, urinary metabolite levels are strongly influenced by differences in the intestinal microbiota, since both gut bacterial metabolism, and shared metabolism by the host and bacterial species ('co-metabolism'), generate specific metabolic products. Such metabolites may therefore be used as markers of microbial metabolic activity, reflecting systemic, functional differences. This application of urinary metabolic profiling avoids the technical difficulties, and methodological differences, found in molecular studies of the intestinal microbiota in IBD, which have contributed to often discrepant findings. Specific urinary metabolites related to gut microbial metabolism differ between CD patients, UC patients, and controls. The emerging technique of urinary NMR-based metabolic profiling with multivariate analysis was able to distinguish these cohorts. This study should address the question, whether VSL#3 administration changes the nuclear magnetic resonance-based urinary metabolomic profile.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Arm CD resected

  • confirmed diagnosis of Crohn´s disease (at least 6 months)
  • history of single resection of terminal ileum (at least 6 months before inclusion)
  • maximum length of resected ileum is 60 cm
  • no signs of disease activity (clinical, endoscopical, laboratory)
  • stable medication

Arm UC unoperated

  • confirmed diagnosis of ulcerative colitis (at least 6 months)
  • no signs of disease activity (clinical, endoscopical, laboratory)
  • stable medication

Arm UC IPAA

  • confirmed diagnosis of ulcerative colitis (at least 6 months)
  • proctocolectomy and IPAA (at least 3 months before inclusion)
  • no signs of disease activity (clinical, endoscopical, laboratory)
  • stable medication

Arm Healthy volunteers

  • no signs of gastrointestinal disorder
  • initial laboratory examination within normal range (blood count, liver function tests, C-reactive protein, Fe, ferritin, fecal calprotectin)

Exclusion Criteria:

  • use of bile acids
  • use of bile acids sequestrants
  • use of farnesoid X receptor agonists/antagonists
  • recent colonoscopy(less than 1 month before inclusion)
  • diabetes
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01765439

Contacts
Contact: Dana Duricova, MD, Ph.D. + 420234770299 ext 222 Dana.Duricova@seznam.cz
Contact: Martin Lenicek, MD, Ph.D. + 420224964199 mleni@centrum.cz

Locations
Czech Republic
Iscare I.V.F. Recruiting
Prague, Czech Republic, 17004
Contact: Dana Duricova, MD, Ph.D.    +420234770299 ext 222    Dana.Duricova@seznam.cz   
Principal Investigator: Dana Duricova, MD, Ph.D         
Sub-Investigator: Milan Lukas, Prof, MD         
Sub-Investigator: Martin Bortlik, MD, Ph.D.         
Sub-Investigator: Nadezda Machkova, MD         
Sub-Investigator: Martin Lukas, MD         
Sub-Investigator: Veronika Hruba, MD         
Sponsors and Collaborators
Charles University, Czech Republic
Iscare i.v.f., Czech Republic
CD Investments srl
University Of Perugia
University of Roma La Sapienza
Investigators
Principal Investigator: Martin Lenicek, MD, Ph.D. Charles University, Czech Republic
  More Information

No publications provided

Responsible Party: Martin Lenicek, assistant professor, Charles University, Czech Republic
ClinicalTrials.gov Identifier: NCT01765439     History of Changes
Other Study ID Numbers: VSL#3-2013-CR
Study First Received: January 7, 2013
Last Updated: March 5, 2014
Health Authority: Czech Republic: Ethics Committee

Keywords provided by Charles University, Czech Republic:
bile acids
metabolism
probiotics

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Crohn Disease
Inflammatory Bowel Diseases
Intestinal Diseases
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Pathologic Processes
Bile Acids and Salts
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014