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Primary Sclerosing Cholangitis With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects (PSC)

Primary Purpose

Primary Sclerosing Cholangitis

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Oral Vancomycin
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis focused on measuring Inflammation of the bile ducts, biliary scarring, obstruction

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • PSC Diagnosis: Liver biopsy and/or imaging (MRCP, ERCP, CT, or US
  • Colonoscopy within 1 year or starting of study

  • 2 groups:

    1. IBD (Inflammatory bowel disease) and PSC: details of extent and type of IBD
    2. No IBD and PSC, but positive p-ANCA or ASCA serologies indicating possible IBD.

Exclusion Criteria:

  • Allergy to Vancomycin
  • PSC not associated with IBD or NO positive IBD antibodies (p-ANCA [anti- neutrophil cytoplasmic antibody] or ASCA [anti-Saccharomyces cerevisiae antibody])
  • Cholangiocarcinoma
  • On oral or topical (enemas or suppositories) corticosteroids,topical mesalamine, or biologics (infliximab, adalimumab, certolizumab).

Sites / Locations

  • Stanford University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Oral Vancomycin

Arm Description

1) For children who weight < or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study. 2) For adults and children who weigh >30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.

Outcomes

Primary Outcome Measures

Count of Participants With Elevated Alanine Aminotransferase (ALT) at Baseline and With Clinically Significant Improvement at Month 3
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Count of Participants With Elevated Gamma-glutamyltransferase (GGT) at Baseline and With Clinically Significant Improvement at Month 3
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated GGT was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Count of Participants With Elevated ALT and/or GGT at Baseline and With Clinically Significant Improvement at Month 3
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT (and GGT) was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Count of Participants With Abnormal Magnetic Resonance Cholangiopancreatography (MRCP) Imaging at Baseline and With Clinically Significant Improvement at Year 1
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis.
Count of Participants With Abnormal Liver Biopsies at Baseline and With Clinically Significant Improvement at Year 1
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis).
Count of Participants With Abnormal MRCP and/or Liver Biopsy at Baseline and With Clinically Significant Improvement at Year 1
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis).

Secondary Outcome Measures

Full Information

First Posted
February 21, 2013
Last Updated
August 23, 2018
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT01802073
Brief Title
Primary Sclerosing Cholangitis With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects
Acronym
PSC
Official Title
Treatment of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
January 2012 (Actual)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Determine the benefit of oral vancomycin therapy for Primary Sclerosing Cholangitis.
Detailed Description
The purpose of this study is to evaluate changes in the fecal and salivary/urinary microbiota during vancomycin treatment of children and adults with Primary Sclerosing Cholangitis (PSC), identify features of the host microbiota that are associated with disease activity and/or response to treatment and further delineate the immunological effects of oral vancomycin treatment of PSC. This study will correlate changes in microbiota with the immunological effects of oral vancomycin in children and adults with PSC. The results of this proposal will lead to new and validated targets for diagnosis and treatment of PSC that will have high impact in the short and long term for patients and their families. Interim results were published in Abarbanel et al, J Clin Immunol 2013 (see References).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
Keywords
Inflammation of the bile ducts, biliary scarring, obstruction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oral Vancomycin
Arm Type
Experimental
Arm Description
1) For children who weight < or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study. 2) For adults and children who weigh >30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Intervention Type
Drug
Intervention Name(s)
Oral Vancomycin
Other Intervention Name(s)
Vancocin
Primary Outcome Measure Information:
Title
Count of Participants With Elevated Alanine Aminotransferase (ALT) at Baseline and With Clinically Significant Improvement at Month 3
Description
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Time Frame
Baseline; Month 3
Title
Count of Participants With Elevated Gamma-glutamyltransferase (GGT) at Baseline and With Clinically Significant Improvement at Month 3
Description
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated GGT was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Time Frame
Baseline; Month 3
Title
Count of Participants With Elevated ALT and/or GGT at Baseline and With Clinically Significant Improvement at Month 3
Description
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT (and GGT) was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Time Frame
Baseline; Month 3
Title
Count of Participants With Abnormal Magnetic Resonance Cholangiopancreatography (MRCP) Imaging at Baseline and With Clinically Significant Improvement at Year 1
Description
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis.
Time Frame
Baseline; Year 1
Title
Count of Participants With Abnormal Liver Biopsies at Baseline and With Clinically Significant Improvement at Year 1
Description
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis).
Time Frame
Baseline; Year 1
Title
Count of Participants With Abnormal MRCP and/or Liver Biopsy at Baseline and With Clinically Significant Improvement at Year 1
Description
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis).
Time Frame
Baseline; Year 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: PSC Diagnosis: Liver biopsy and/or imaging (MRCP, ERCP, CT, or US Colonoscopy within 1 year or starting of study 2 groups: IBD (Inflammatory bowel disease) and PSC: details of extent and type of IBD No IBD and PSC, but positive p-ANCA or ASCA serologies indicating possible IBD. Exclusion Criteria: Allergy to Vancomycin PSC not associated with IBD or NO positive IBD antibodies (p-ANCA [anti- neutrophil cytoplasmic antibody] or ASCA [anti-Saccharomyces cerevisiae antibody]) Cholangiocarcinoma On oral or topical (enemas or suppositories) corticosteroids,topical mesalamine, or biologics (infliximab, adalimumab, certolizumab).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth Cox, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23054338
Citation
Abarbanel DN, Seki SM, Davies Y, Marlen N, Benavides JA, Cox K, Nadeau KC, Cox KL. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis. J Clin Immunol. 2013 Feb;33(2):397-406. doi: 10.1007/s10875-012-9801-1. Epub 2012 Oct 9.
Results Reference
result
PubMed Identifier
32633158
Citation
Ali AH, Damman J, Shah SB, Davies Y, Hurwitz M, Stephen M, Lemos LM, Carey EJ, Lindor KD, Buness CW, Alrabadi L, Berquist WE, Cox KL. Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Scand J Gastroenterol. 2020 Aug;55(8):941-950. doi: 10.1080/00365521.2020.1787501. Epub 2020 Jul 7.
Results Reference
derived
Links:
URL
http://med.stanford.edu/clinicaltrials/
Description
Stanford Clinical Trials

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Primary Sclerosing Cholangitis With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects

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