Evaluation of an Oral Microbiota-based Therapeutic as a Treatment Option for PSC

University of Minnesota (UMN)

Status and phase

Enrolling

Early Phase 1

Conditions

Primary Sclerosing Cholangitis

Treatments

Drug: oral vancomycin and oral amoxicillin

Study type

Interventional

Funder types

Other

Identifiers

NCT06197308

MED-2023-32551

Details and patient eligibility

About

This pilot clinical trial will evaluate the initial safety and feasibility of microbiota transplant therapy (MTT) inpatients with primary sclerosing cholangitis (PSC). This trial will inform development of future trials in treatment of PSC.

Enrollment

28 estimated patients

Sex

All

Ages

18 to 76 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Ages 18-76
Diagnosis of PSC based on American Association for the Study of Liver Diseases2: serum alkaline phosphatase (ALP) ≥ 1.5x upper limit of normal, cholangiographic evidence for PSC per MRI, endoscopic retrograde cholangiopancreatography, direct cholangiography or liver biopsy for > 6 months in duration
Serum total bilirubin at screening ≤ 2x the upper limit of normal
Absence of biliary obstruction and malignancy by ultrasound or equivalent imaging within 6 months of study entry
Anticipated maintenance of current medication regimen through the treatment period (UDCA, azathioprine, corticosteroid, methotrexate, 5-ASA, biologic therapy and/or probiotic)
3-month washout period of obeticholic acid or other experimental therapies for PSC
Stated willingness to comply with all study procedures and availability for the duration of trial to follow-up by telephone, in-person, email, and/or video visits or correspondence.
Informed consent

Exclusion criteria

Antibiotic therapy (except vancomycin) within 3 months or anticipated antibiotic use in the course of the MTT treatment
Presence of complications of advanced PSC, such as hepatic encephalopathy, ascites, history of esophageal varices, portal hypertension, hepato-renal syndrome, portopulmonary syndrome, and hepato-pulmonary syndrome
Evidence for viral hepatitis (history of Hepatitis C is eligible with undetectable HCV RNA); HIV/AIDS
Metabolic or inherited liver disease (e.g., Wilson's, hemochromatosis, alpha-1-antitrypsin deficiency)
Another disease involving bile ducts (e.g., primary biliary cholangitis, IgG4-related cholangitis, secondary sclerosing cholangitis)
Evidence of cirrhosis on the last magnetic resonance cholangiopancreatography (within 6 months)
Pregnancy or attempting to become pregnant or breastfeeding.
History of liver transplantation, anticipated need for liver transplantation within 12- months from randomization, or a Model of End Stage Liver Disease (MELD) score of ≥15
Active malignancy
Active alcohol overuse (>4 drinks per day for men, and >2 drinks per day for women)
Moderate-to-severe renal impairment with a calculated creatinine clearance of < 45 mL/min
Neutropenia (an absolute neutrophil count < 0.5 x 109 cells/L)
History of allergic reaction to vancomycin
History of allergic reaction to amoxicillin or other beta-lactam antibiotics
Any other conditions or abnormalities that, in the opinion of the investigator, may compromise the safety of the subject or interfere with the subject participating in or completing the study