Probiotics in Patients With Primary Sclerosing Cholangitis
Primary Purpose
Primary Sclerosing Cholangitis
Status
Unknown status
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Probiotics
Sponsored by
About this trial
This is an interventional treatment trial for Primary Sclerosing Cholangitis focused on measuring PSC, Liver biochemistry, Probiotics, Pruritus
Eligibility Criteria
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
Sites / Locations
- UMC UtrechtRecruiting
Outcomes
Primary Outcome Measures
Assessment of the effects of treatment with probiotics on serum liver tests
Secondary Outcome Measures
Assessment of the effects of treatment with probiotics on fatigue and pruritus
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00161148
Brief Title
Probiotics in Patients With Primary Sclerosing Cholangitis
Official Title
Probiotics in Patients With Primary Sclerosing Cholangitis and Inflammatory Bowel Disease- a Randomized Placebo-Controlled Cross-Over Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2007
Overall Recruitment Status
Unknown status
Study Start Date
January 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 2006 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
UMC Utrecht
4. Oversight
5. Study Description
Brief Summary
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
Keywords
PSC, Liver biochemistry, Probiotics, Pruritus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
Double
Allocation
Randomized
Enrollment
12 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Probiotics
Primary Outcome Measure Information:
Title
Assessment of the effects of treatment with probiotics on serum liver tests
Secondary Outcome Measure Information:
Title
Assessment of the effects of treatment with probiotics on fatigue and pruritus
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karel v Erpecum, MD, PhD
Phone
+31 30 2506275
Email
k.j.vanerpecum@azu.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Frank Vleggaar, MD, PhD
Phone
+ 31 30 2506275
Email
f.vleggaar@azu.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karel v Erpecum, MD, PhD
Organizational Affiliation
UMC Utrecht
Official's Role
Principal Investigator
Facility Information:
Facility Name
UMC Utrecht
City
Utrecht
ZIP/Postal Code
3508 GA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karel v Erpecum, MD, PhD
Phone
+31 302506275
Email
k.j.vanerpecum@azu.nl
First Name & Middle Initial & Last Name & Degree
Karel v Erpecum, MD, PhD
12. IPD Sharing Statement
Citations:
PubMed Identifier
15122774
Citation
Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology. 2004 May;39(5):1441-9. doi: 10.1002/hep.20194.
Results Reference
background
PubMed Identifier
9041099
Citation
Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med. 1997 Mar 6;336(10):691-5. doi: 10.1056/NEJM199703063361003.
Results Reference
background
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Probiotics in Patients With Primary Sclerosing Cholangitis
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