ActivePhase 3ACTRN12621000792820

Targeting the gut microbiome as a treatment for Primary Sclerosing Cholangitis: The Queensland Clinical Network Study

The impact of targeting the gut microbiome on improvement in liver function in individuals with Primary Sclerosing Cholangitis: The Queensland Clinical Network Study.

Sponsor

Princess Alexandra Hospital

Enrollment

50 participants

Start Date

Jun 14, 2022

Study Type

Interventional

Conditions

Primary Sclerosing Cholangitis

Summary

Primary sclerosing cholangitis (PSC) is a progressive, chronic liver disease leading to end stage liver-failure with limited treatment options. Case series and a recent systematic review and meta-analysis found that antibiotic therapy and in particular treatment with the non-absorbable antibiotic vancomycin was associated with substantial clinical improvement or even remission of PSC and the concomitant inflammation of the bowel. Against this background we aim in a placebo-controlled trial in PSC patients with and without concomitant IBD to define the effects of antibiotic therapy on disease activity. It is hypothesised that targeted modulation of the microbiota with vancomycin will improve clinical outcomes for these patients.

Eligibility

Sex: Both males and femalesMin Age: 14 YearssMax Age: 74 Yearss

Inclusion Criteria7

Male and females (females of childbearing age must have negative pregnancy test within 48 hours of participation and agreement to practice contraception for the duration of the study), age =>14 years old and <75 years,
Established clinical diagnosis of PSC (confirmed by a hepatologist) with or without an associated IBD
o History of chronic cholestatic disease of at least 6 months duration,
o Serum alkaline phosphatase level at least 1.5 times the upper limit of normal.
o Cholangiography or MRCP demonstrating intrahepatic and/or extrahepatic biliary obstruction, beading, or narrowing consistent with PSC (without evidence for other causes of the biliary abnormalities).
Patients have given informed consent for study participation.
All other treatments for PSC and IBD need to be stable for the last 4 weeks prior to inclusion.

Exclusion Criteria8

Findings highly suggestive of hepatobiliary disease of other aetiology complicating PSC,
Anticipated need for liver transplantation in one year (e.g. determined by Mayo model with an estimate of <75% one year survival without transplantation),
Recurrent variceal bleeding, presence of ascites, or encephalopathy,
Active drug or alcohol use, pregnancy, breast feeding,
Serum creatinine over 1.5 fold of the norm,
Prior history of allergic reactions to antibiotics belonging to the family to be used,
Any condition that, in the opinion of the investigator, would interfere with the patient's ability to complete the study safely or successfully.
Evidence of active malignancy.

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Interventions

This is a 52 week, multi-center, randomised placebo-controlled trial (RCT) with a cross over design where 34 patients with PSC, with and without an associated IBD will be randomized to either oral vancomycin or placebo treatment, in a 1:1 ratio. Patients will receive 250 mg vancomycin capsules orally or ONE placebo capsule twice daily for 12 weeks. Adherance to intervention will not be monitored in this study. There is no washout period between the arms.