Vancomycin for Primary Sclerosing Cholangitis

• ClinicalTrials.gov Identifier: NCT03710122
• Recruitment Status: Recruiting
• First Posted: October 17, 2018
• Last Update Posted: August 29, 2022
• Sponsor: Elizabeth Carey
• Collaborator: Arizona State University
• Information provided by (Responsible Party): Elizabeth Carey, Mayo Clinic

Study Description

Brief Summary:

To find out if vancomycin is a safe and effective therapy for primary sclerosing cholangitis.

Funding Source - FDA OOPD

Condition or disease	Intervention/treatment	Phase
Primary Sclerosing Cholangitis	Drug: Vancomycin; Other: Placebo	Phase 2; Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Multi-centered, Placebo-controlled Clinical Trial of Oral Vanycomycin in Adults With Primary Sclerosing Cholangitis
• Actual Study Start Date: January 23, 2020
• Estimated Primary Completion Date: October 30, 2024
• Estimated Study Completion Date: November 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vancomycin	Drug: Vancomycin; Firvanq by Azurity Pharmaceuticals, Inc.
Placebo Comparator: Placebo	Other: Placebo; Placebo for Vancomycin

Outcome Measures

Primary Outcome Measures :

1. Alkaline phosphatase at 6 months [ Time Frame: 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.
2. Alkaline phosphatase at 12 months [ Time Frame: 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.
3. Alkaline phosphatase at 18 months [ Time Frame: 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.
4. Alkaline phosphatase at 3 months post treatment = 21 months [ Time Frame: 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.
5. Alkaline phosphatase at 6 months post treatment = 24 months [ Time Frame: 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.

Secondary Outcome Measures :

1. Fibroscan, cholangiography [ Time Frame: 18 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 76 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 α-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 complications of advanced PSC such as hepatic encephalopathy, portal hypertension, 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.

Contacts and Locations

Contacts

Contact: Aatikah Mouti; 408-342-2479; Mouti.Aatikah@mayo.edu

Locations

United States, Arizona

Mayo Clinic Arizona; Recruiting

Phoenix, Arizona, United States, 85259

Contact: Elizabeth Carey, MD 480-342-1094

Arizona State University; Active, not recruiting

Tempe, Arizona, United States, 85281

United States, Florida

Mayo Clinic Florida; Recruiting

Jacksonville, Florida, United States, 32224

Contact: Denise M Harnois, DO 904-956-3258

United States, Minnesota

Mayo Clinic Rochester; Recruiting

Rochester, Minnesota, United States, 55905

Contact: John Eaton, MD 507-284-3917

Sponsors and Collaborators

Elizabeth Carey

Arizona State University

Investigators

• Principal Investigator: Elizabeth Carey, MD; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Elizabeth Carey, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03710122
• Other Study ID Numbers: IND133287; FD-R-6102 ( Other Grant/Funding Number: FDA OOPD )
• First Posted: October 17, 2018
• Last Update Posted: August 29, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cholangitis; Cholangitis, Sclerosing; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Vancomycin; Anti-Bacterial Agents; Anti-Infective Agents