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

Primary Sclerosing Cholangitis Clinical Trial

Official title:

Evaluation of an Oral Microbiota-based Therapeutic as a Treatment Option for Primary Sclerosing Cholangitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06197308
• Other study ID #: MED-2023-32551
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 1, 2024
• Est. completion date: September 1, 2025

Study information

• Verified date: March 2024
• Source: University of Minnesota
• Contact: Amanda Kabage
• Email: kabage[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: September 1, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 76 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• oral vancomycin and oral amoxicillin
In this study, PSC patients will receive an antibiotic preconditioning regimen of oral vancomycin (500 mg liquid twice a day) for 28 days and oral amoxicillin (1000 mg twice a day) for 7 days (during the last 7 days of the oral vancomycin). Following vancomycin and amoxicillin, encapsulated, freeze-dried microbiota preparation (MTP-101C) will be administered - dosed at = 5 x 10^11 bacteria (five capsules) daily for 3 days followed by = 2 x 10^11 bacteria (two capsules) for 11 days - for a total of 14 days of MTP-101C; total of 37 capsules.

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate safety of MTT in patients with PSC	Determine the frequency of serious adverse events and other adverse events	221 days
Primary	To evaluate feasibility of MTT in patients with PSC	Determine proportion of subjects taking 100% of the MTT per protocol.	221 days