None listed
Conditions
Brief summary
Primary sclerosing cholangitis (PSC) is a rare and chronic liver disease with no current effective medical treatment options. Patients with PSC are at high risk of bile duct cancer, recurrent sepsis, and many progress to liver transplantation within 10 years. Patients with PSC have an abnormal gut microbiota and current evidence suggests that manipulation of the gut microbiota holds promise as a therapeutic strategy in PSC. The proposed study is investigating whether faecal microbiota transplantation (FMT) from healthy donors, delivered via lyophylised (freeze-dried) capsules, is safe for patients with PSC. The study will also seek signals for efficacy in terms of improving liver function tests and liver duct changes visible on imaging. Participants who choose to enrol in the sub-study will undergo endoscopic-ultrasound guided portal vein sampling at the time of their baseline and week 24 colonoscopies. The sub-study aims to identify the composition and function of the microbiota of the portal venous system and their products, and to explore how this is altered by FMT. This may reveal important pathogenic links between the gut and the liver in PSC, which can be used to develop future therapies.
Interventions
Faecal microbiota transplantation capsules:
a) 6 capsules per day in the 2 week induction period (amounting to approximately 4 grams of stool per day)
b) followed by 2 capsules per day during the 22 week maintenance period (amounting to approximately 1.3 grams of stool per day)
Adherence to treatment will be measured using a self-reporting as well as return of capsules.
The sub-study will not involve an additional intervention or exposure, but will involve additional samples to be taken, inclu
Faecal microbiota transplantation capsules: a) 6 capsules per day in the 2 week induction period (amounting to approximately 4 grams of stool per day) b) followed by 2 capsules per day during the 22 week maintenance period (amounting to approximately 1.3 grams of stool per day) Adherence to treatment will be measured using a self-reporting as well as return of capsules. The sub-study will not involve an additional intervention or exposure, but will involve additional samples to be taken, including portal venous blood, peripheral blood, stool and urine and baseline and at 24 weeks after study enrolment.
Sponsors
BiomeBank
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of PSC (small and large-duct) established for 6 months or more 2. Age 16-75 years 3. If taking ursodeoxycholic acid then stable dose at less than 25mg/kg/day for more than 12 weeks prior to study entry 4. Laboratory parameters: o ALP elevated above the upper limit of normal (above 110 U/L) o International normalized ratio less than or equal to 1.3 o eGFR more than 60mL/min/1.73m2 o Albumin more than 32 g/L o Platelets more than 120 x 109/L
Exclusion criteria
• Serum ALP variation > 30% between tests at two time-points 1 week apart during screening (unless both figures within normal range) • Childs B or C cirrhosis (clinical parameters as assessed by the treating clinician) or clinically significant portal hypertension • Total bilirubin > 1.5 x ULN unless due to Gilbert’s syndrome • Liver transplantation • Subtotal or total colectomy • Active malignancy (cholangiocarcinoma or colorectal cancer) • Presence of positive antimitochondrial antibody or features to suggest overlap autoimmune hepatitis • Clinically significant dominant stricture deemed likely to require intervention within 3 months • Ascending cholangitis within 3 months prior to enrolment • Presence of a percutaneous drain or biliary stent • Other causes of liver disease (alcohol induced hepatitis, viral hepatitis, primary biliary cholangitis, hemochromatosis, Wilson’s disease, Alpha-1 antitrypsin deficiency, non-alcoholic fatty liver disease) • Pregnant or intending to become pregnant within 24 weeks • Currently breastfeeding • Immunodeficiency (beyond that associated with IBD-related therapy) • Prebiotic, probiotic or antibiotic use within 4 weeks of enrolment • Allergy or intolerance to vancomycin, metronidazole or neomycin • Corticosteroid therapy of prednisolone >25mg daily (or equivalent) • Anticoagulant therapy or dual antiplatelet therapy • Active illicit drug use, narcotic drug use or alcohol consumption of a dependent nature • Active IBD which has required change in therapy in the last 3 months or thought to require change in medication or surgery within 3 months of study entry • Any medical condition that the treating gastroenterologist deems to pose a theoretical risk to the participant undergoing FMT • Past colonic dysplasia apart from low grade dysplasia arising in tubular adenoma or sessile serrated adenoma • Presence of IgG4-related disease • Anaphylaxis to any food products • Coeliac disease • Participant unable to provide informed consent For those enrolling in the sub-study, additional exclusion criteria include: • Any medical conditions which increase the risk of bleeding including haemophilia or other known specific clotting factor deficiencies • Portal vein thrombosis • Portal hypertension (clinically, on FibroScan, endoscopic features, or endoscopic ultrasound features)
Outcome results
None listed