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

Ulcerative Colitis Clinical Trial

Official title:

The Effect of VSL#3 (Original De Simone Formulation) Probiotic Preparation on the Bile Acid Metabolism in Patients With Inflammatory Bowel Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01765439
• Other study ID #: VSL#3-2013-CR
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 2014
• Est. completion date: March 2025

Study information

• Verified date: August 2023
• Source: Charles University, Czech Republic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 79
• Est. completion date: March 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases
• Ulcerative Colitis

Intervention

Dietary Supplement:
• VSL#3 (Original De Simone formulation)
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).

Locations

Country	Name	City	State
Czechia	Iscare I.V.F.	Prague

Sponsors (5)

Lead Sponsor	Collaborator
Charles University, Czech Republic	CD Investments srl, Iscare i.v.f., Czech Republic, University Of Perugia, University of Roma La Sapienza

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of the disease activity		Baseline and 6 weeks (plus or minus 5 days).
Primary	Alteration in the rate of bile acid synthesis	Will be assessed as difference between serum levels of fibroblast growth factor 19 and C4 at baseline and 6 weeks, respectively.	Baseline and 6 weeks (plus or minus 5 days)
Secondary	Change of the spectrum of bile acids in stools and plasma		Baseline and 6 weeks (plus or minus 5 days).
Secondary	Change of a metabolomic profile in urine		Baseline and 6 weeks (plus or minus 5 days).