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

January 7, 2013
March 5, 2014
February 2014
December 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01765439 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Change of the disease activity [ Time Frame: Baseline and 6 weeks (plus or minus 5 days). ] [ Designated as safety issue: No ]
Same as current
 
The Effect of VSL#3 Probiotic Preparation on the Bile Acid Metabolism in Patients With Inflammatory Bowel Disease
The Effect of VSL#3 Probiotic Preparation on the Bile Acid Metabolism in Patients With Inflammatory Bowel Disease

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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
  • Crohn Disease
  • Ulcerative Colitis
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: CD resected
    Patients with Crohn´s disease with the history of single resection (<60 cm) of distal leum.
    Intervention: Dietary Supplement: VSL#3
  • Experimental: UC unoperated
    Patients with ulcerative colitis without history of gut resection.
    Intervention: Dietary Supplement: VSL#3
  • Experimental: UC IPAA
    Patients with ulcerative colitis after proctocolectomy and ileal pouch-anal anastomosis(IPAA).
    Intervention: Dietary Supplement: VSL#3
  • Experimental: Healthy volunteers
    Subjects without any sign of disease of the digestive tract.
    Intervention: Dietary Supplement: VSL#3
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
February 2015
December 2014   (final data collection date for primary outcome measure)

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
Both
Not Provided
Yes
Contact: Dana Duricova, MD, Ph.D. + 420234770299 ext 222 Dana.Duricova@seznam.cz
Contact: Martin Lenicek, MD, Ph.D. + 420224964199 mleni@centrum.cz
Czech Republic
 
NCT01765439
VSL#3-2013-CR
No
Martin Lenicek, Charles University, Czech Republic
Charles University, Czech Republic
  • Iscare i.v.f., Czech Republic
  • CD Investments srl
  • University Of Perugia
  • University of Roma La Sapienza
Principal Investigator: Martin Lenicek, MD, Ph.D. Charles University, Czech Republic
Charles University, Czech Republic
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP