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

NCT01802073 | Completed Phase 3 Results DMC

• 1 other identifier: 22591
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Determine the benefit of oral vancomycin therapy for Primary Sclerosing Cholangitis.

Conditions

Primary Sclerosing Cholangitis

Keywords

Inflammation of the bile ducts; biliary scarring; obstruction

Outcome Measures

Primary Outcomes (6)

• 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.

  Baseline; Month 3

• 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.

  Baseline; Month 3

• 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.

  Baseline; Month 3

• 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.

  Baseline; Year 1

• 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).

  Baseline; Year 1

• 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).

  Baseline; Year 1

Study Arms (1)

Oral Vancomycin

EXPERIMENTAL

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.

Drug: Oral Vancomycin

Interventions

Oral Vancomycin DRUG

Also known as: Vancocin

Oral Vancomycin

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Related Publications (2)

• 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.

  PMID: 23054338 RESULT

• 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.

  PMID: 32633158 DERIVED

Related Links

• Stanford Clinical Trials

MeSH Terms

Conditions

Cholangitis, Sclerosing; Bites and Stings

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Kenneth Cox
• Organization: Stanford University

KCox@stanfordchildrens.org

(650) 723-5070

Study Officials

• Kenneth Cox, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: March 1, 2013
• Study Start: January 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: September 21, 2018
• Results First Posted: September 21, 2018

Record last verified: 2018-08

Locations

US (1)