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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: oral vancomycin and oral amoxicillin

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Amanda Kabage; Email: kabage@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • University of Minnesota
      • Contact: Amanda Kabage; Email: kabage@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PCS patients

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.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Elizabeth Aby, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: December 26, 2023
• First Submitted That Met QC Criteria: December 26, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Amoxicillin
• Other Study ID Numbers: MED-2023-32551

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No