Clinical trial NCT01765439: The Effect of VSL#3 Probiotic Preparation on the Bile Acid Metabolism in Patients With Inflammatory Bowel Disease
Official title: The Effect of VSL#3 (Original De Simone Formulation) Probiotic Preparation on the Bile Acid Metabolism in Patients With Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Crohn Disease
Ulcerative Colitis
Keywords: bile acids
metabolism
probiotics
Lead sponsor: Charles University, Czech Republic
Sponsor class: OTHER
Collaborators: name: Iscare i.v.f., Czech Republic
name: CD Investments srl
name: University Of Perugia
name: University of Roma La Sapienza
First posted: 2013-01-10
Enrollment: 79
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of the study is to determine, whether administration of VSL#3 (Original De Simone formulation) probiotic preparation can alter the bile acid metabolism in patients with inflammatory bowel disease.

Detailed description: VSL#3 (Original De Simone formulation, further abbreviated as 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 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

Primary outcomes:
measure: Alteration in the rate of bile acid synthesis
timeFrame: Baseline and 6 weeks (plus or minus 5 days)
Secondary outcomes:
measure: Change of the spectrum of bile acids in stools and plasma
timeFrame: Baseline and 6 weeks (plus or minus 5 days).
measure: Change of a metabolomic profile in urine
timeFrame: Baseline and 6 weeks (plus or minus 5 days).
Other outcomes:
measure: Change of the disease activity
timeFrame: Baseline and 6 weeks (plus or minus 5 days).
Locations:
city: Prague
country: Czechia
facility: Iscare I.V.F.
Study officials:
affiliation: Charles University, Czech Republic
name: Martin Lenicek, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: