Probiotics in Patients With Primary Sclerosing Cholangitis

January 8, 2007 updated by: UMC Utrecht

Probiotics in Patients With Primary Sclerosing Cholangitis and Inflammatory Bowel Disease- a Randomized Placebo-Controlled Cross-Over Trial

PSC is a progressive liver disease without effective medical treatment. There is often co-existent ulcerative colitis. Probiotics (bacterial food supplements) have been shown to benefit patients with ulcerative colitis. In the current protocol potential beneficial effects of probiotics on liver biochemistry and liver related symptoms as pruritus are being assessed in 12 PSC patients in a randomized controlled cross over study (3 months probiotics, 1 one wash-out and 3 months placebo).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

I. INTRODUCTION Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease characterized by multifocal strictures of intrahepatic and extrahepatic bile ducts, which frequently leads to biliary cirrhosis and liver failure. The aetiology of PSC is unknown but is thought to be (auto)immune-mediated. Nevertheless, in a number of randomized controlled trials a clear benefit of treatment with various immunosuppressive agents, such as D-penicillamine, methotrexate, corticosteroids or nicotine, could not be demonstrated. Although treatment with ursodeoxycholic acid (UDCA) improves serum liver tests and is prescribed on a large scale for PSC patients, this therapeutic modality may have no beneficial effect on the course of the disease.

70 - 90% of patients with PSC have concurrent inflammatory bowel disease (IBD), mostly ulcerative colitis. Conversely, 7% of patients with IBD have PSC. The close association between inflammatory bowel disease and PSC suggests that substances originating from the inflamed gut may damage the liver and biliary tree. Bacterial products may act as toxic proinflammatory agents. N-formyl L-methionine L-leucine L-tyrosine is a peptide produced by enteric flora. When this peptide was introduced into the colon of rats with colitis, it was absorbed, underwent enterohepatic circulation, and appeared undegraded in bile. Histologic changes in the livers of the rats resembled those in PSC.

Probiotics are beneficial bacteria that are used to redress the bacterial composition of the enteric flora which may be altered in disease. Beneficial effects of probiotics have already been described in diseases such as inflammatory bowel disease, pouchitis and non-alcoholic fatty liver disease. Probiotic bacteria have also been shown to counteract inflammatory processes by enhancing the degradation of enteral antigens, reducing the secretion of inflammatory mediators, thereby modifying in a beneficial way the balance between pro- and anti-inflammatory mediators, and stabilizing gut barrier functions. These effects may benefit PSC patients.

Our hypothesis is that administration of probiotics may improve the composition of the enteric flora and subsequently decrease the release of substances that may be toxic and harmful for the liver and biliary tree in PSC patients. Furthermore, immunological alterations induced by treatment with probiotics may have positive effects in PSC.

II. AIM OF THE STUDY Primary aim: assessment of the effects of treatment with probiotics on serum liver tests.

Secondary aim: assessment of the effects of treatment with probiotics on fatigue and pruritus.

III. DESIGN OF THE STUDY Double-blind randomized cross-over pilot study. Eligible patients will be randomized to treatment with probiotics or placebo for a period of 12 weeks. After a wash-out period of 4 weeks, placebo-treated patients will receive verum and vice versa for another period of 12 weeks.

Dosage of concurrent medication for PSC (UDCA, immunosuppressives) will remain the same during the entire study period.

Patients who are being treated with antibiotics during the study period for more than 1 week will be withdrawn from the study.

Study Type

Interventional

Enrollment

12

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Frank Vleggaar, MD, PhD
  • Phone Number: + 31 30 2506275
  • Email: f.vleggaar@azu.nl

Study Locations

  • Netherlands
      • Utrecht, Netherlands, 3508 GA
        • Recruiting
        • UMC Utrecht
        • Contact:
        • Principal Investigator:
          • Karel v Erpecum, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of PSC based on characteristic findings on cholangiography, or based on the triad: typical histological findings in a liver biopsy, elevated serum alkaline phosphatase and presence of inflammatory bowel disease
  • Presence of inflammatory bowel disease
  • elevated serum alkaline phosphatase
  • age ≥ 18 years
  • informed consent

Exclusion Criteria:

  • Pregnancy
  • use of probiotics within one month before the study
  • use of antibiotics within one month before the study
  • a history of bacterial cholangitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Assessment of the effects of treatment with probiotics on serum liver tests

Secondary Outcome Measures

Outcome Measure
Assessment of the effects of treatment with probiotics on fatigue and pruritus

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UMC Utrecht

Investigators

  • Principal Investigator: Karel v Erpecum, MD, PhD, UMC Utrecht

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Study Completion

May 1, 2006

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Estimate)

January 9, 2007

Last Update Submitted That Met QC Criteria

January 8, 2007

Last Verified

January 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PBPSC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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