Vancomycin for Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis Clinical Trial

Official title:

A Prospective, Randomized, Multi-centered, Placebo-controlled Clinical Trial of Oral Vanycomycin in Adults With Primary Sclerosing Cholangitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03710122
• Other study ID #: 18-003439
• Secondary ID: FD-R-6102
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 23, 2020
• Est. completion date: November 30, 2026

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: Latasha Bunkley
• Phone: 408-342-5756
• Email: Bunkley.Latasha[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To find out if vancomycin is a safe and effective therapy for primary sclerosing cholangitis. Funding Source - FDA OOPD

Description:

A. Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 6,12,and 18 months of OV treatment, and at 3, and 6 months post OV treatment will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm. B. Determine if OV stabilizes or improves liver fibrosis assessed by LSM using TE. Liver stiffness will be measured at 6, 12, and 18 months of OV treatment, and at 6 months post OV treatment, and values will be compared to those obtained at baseline (month 0), and with values in the placebo arm. C. Determine the changes in the intestinal microbiota in relation to the use of OV, and study the correlation between the changes in the intestinal microbiota and the changes in: 1) liver enzymes, particularly serum ALP, and 2) liver stiffness, assessed by LSM using TE. D. Determine if changes in proinflammatory cytokines (TGF-β, IL-4, IL-13, IL-10, etc.) predict response to OV. Cytokines will be measured at baseline, months 6, 12, 18, and at 3, and 6 months post OV treatment, if the study is positive.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: November 30, 2026
• Est. primary completion date: October 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 76 Years

Eligibility

Inclusion Criteria:

1. Male or female subject age 18-76 years

2. Diagnosis of PSC consistent with the guidelines published by the American Association for the Study of Liver Diseases (AASLD).39 All subjects must have an elevated serum ALP of at least 1.5 times upper limit of normal at baseline plus cholangiographic evidence of PSC, as demonstrated by magnetic resonance imaging, endoscopic retrograde cholangiography, direct cholangiography, or liver biopsy.

3. Total bilirubin at screening must be = 2 times upper limit of normal

4. An ultrasound (or equivalent imaging modality) that excludes biliary obstruction and malignancy within 6 months of study entry,

5. If a patient is on any of the following medications and/or supplements, he or she is expected to remain on the same daily dose through the treatment period: UDCA, azathioprine, prednisone (or an equivalent steroid compound), methotrexate, a 5-aminosalicylic acid, biologic therapy, and/or a probiotic.

6. If a patient has been on obeticholic acid or other experimental therapies for PSC, they must complete a 3 month washout period before study entry

7. PSC with or without inflammatory bowel disease, such as ulcerative colitis or Crohn's disease

8. Must agree to comply with the study protocol and provide informed consent.

Exclusion Criteria:

1. Administration of an antibiotic within 3 months prior to the study,

2. Pregnancy or attempting to become pregnant or breastfeeding,

3. Presence of any of the following:

i. Hepatitis B infection ii. Hepatitis C infection (antibody positive); patients with a history of hepatitis C infection will be eligible for this study if they have undetectable levels of HCV RNA iii. Other cholestatic liver diseases such as primary biliary cholangitis and cholestatic diseases of pregnancy iv. Metabolic liver diseases such as Wilson's disease and hemochromatosis v. Inherited diseases of the liver such as a-1 antitrypsin deficiency vi. Immunoglobulin G4-related cholangitis vii. PSC with concomitant autoimmune hepatitis (AIH) and/or primary biliary cholangitis (previously known as primary biliary cirrhosis) viii. Secondary sclerosing cholangitis (SSC), ix. Active acute ascending cholangitis requiring antibiotics x. CCA (malignant biliary stricture, neoplasm, and cytology/histopathology or positive fluorescence in situ hybridization (FISH) consistent with adenocarcinoma of the bile duct) xi. A liver biopsy, if one has been previously obtained, which showed non-alcoholic steatohepatitis (NASH). Patients with suspected fatty liver by imaging will not be excluded xii. Presence of decompensated cirrhosis such as hepatic encephalopathy, hepato-renal syndrome and hepato-pulmonary syndrome, xiii. 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 xiv. Ongoing alcohol abuse (>4 drinks per day for men, and >2 drinks per day for women) xv. History of allergic reaction to vancomycin, xvi. Moderate-to-severe renal impairment with a calculated creatinine clearance of < 60mL/min xvii. HIV/AIDS, xviii. 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:
• Vancomycin
Firvanq by Azurity Pharmaceuticals, Inc.

Other:
• Placebo
Placebo for Vancomycin

Locations

Country	Name	City	State
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Arizona State University	Tempe	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Elizabeth Carey	Arizona State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alkaline phosphatase at 6 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 6 months of OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	6 months
Primary	Alkaline phosphatase at 12 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 12 months of OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	12 months
Primary	Alkaline phosphatase at 18 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 18 months of OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	18 months
Primary	Alkaline phosphatase at 3 months post treatment = 21 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 3 months post OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	21 months
Primary	Alkaline phosphatase at 6 months post treatment = 24 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 6 months post OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	24 months
Secondary	Fibroscan, cholangiography	Transient elastography (TE), a new technique that allows non-invasive assessment and follow up of liver fibrosis by measuring liver stiffness, differentiates between severe from non-severe fibrosis in PSC, and the rate of progression of liver stiffness measurement (LSM) assessed by TE correlates well with the rate of progression of fibrosis in PSC and with patients' clinical outcomes.	18 months