Gastrointestinal Microbiota in Primary Sclerosing Cholangitis and Biliary Atresia With Vancomycin (PSC)

• ClinicalTrials.gov Identifier: NCT01322386
• Recruitment Status: Completed
• First Posted: March 24, 2011
• Results First Posted: March 4, 2016
• Last Update Posted: May 18, 2016
• Sponsor: Stanford University
• Information provided by (Responsible Party): Kenneth L. Cox, Stanford University

Tracking Information

• First Submitted Date: February 10, 2011
• First Posted Date: March 24, 2011
• Results First Submitted Date: May 22, 2015
• Results First Posted Date: March 4, 2016
• Last Update Posted Date: May 18, 2016
• Study Start Date: May 2007
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 5, 2016)

Determine the Benefit of Oral Vancomycin Therapy for Primary Sclerosing Cholangitis and Biliary Atresia [ Time Frame: Within 3 months of therapy ]

Determine the benefit of oral vancomycin therapy for Primary Sclerosing Cholangitis and Biliary Atresia through improvement of Liver function tests (LFTs) within 3 months of initiating therapy. In addition for PSC, we looked at 25% reduction of abnormal ALT & GGT, reduction in biliary strictures and beading, and reduction of inflammation in liver biopsies and colon biopsies.

Original Primary Outcome Measures (submitted: March 23, 2011)

Determine the Benefit of Oral Vancomycin Therapy for Primary Sclerosing Cholangitis and Biliary Atresia [ Time Frame: Within 3 months of therapy ]

Blood tests(liver enzymes - ALT and GGT), imaging studies (MRI, ERCP) and/or liver biopsy changes before and while on oral vancomycin will assess the benefit of the therapy.

• Change History: Complete list of historical versions of study NCT01322386 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gastrointestinal Microbiota in Primary Sclerosing Cholangitis and Biliary Atresia With Vancomycin
• Official Title: The Human Gastrointestinal Tract Microbiota in the Setting of Treating Primary Sclerosing Cholangitis and Biliary Atresia With Vancomycin.

Brief Summary

The goals of the proposed work are two fold:

Firstly, to see if the antibiotic vancomycin may be used for the early treatment of Biliary Atresia (BA) and Primary Sclerosing Cholangitis (PSC). The investigators hope to learn what effect Vancomycin has on the bacteria that are present in stool, body fluid or intestinal tissue on someone who has BA and PSC and if so by what mechanism. Secondly, the investigators hope to learn to characterize human intestinal microbial communities (microbiome: the collection or collectivity of microorganisms) using molecular methods, examine the mechanisms of interaction between host and microbiome using genomic approaches, and determine how the microbiome both preserves local health and promotes pathology. The investigators will focus on primary sclerosing cholangitis, biliary atresia, as well as states of health. The composition of the associated microbiome will be assessed based on ribosomal DNA and RNA sequences, and attention will be given to richness (diversity), evenness (relative abundance), and variation with respect to time, person, and anatomic niche. Host response at the adjacent mucosal surface will be assessed based on genome-wide gene expression patterns.

Detailed Description

As many as 55 subjects (35 with BA or PSC and 20 Controls) will be involved. We are also recruiting 20 adult patients with either BA, or PSC. The patients will be recruited from Lucile Children's Hospital, Stanford Medical Center, and Stanford Redwood City Campus such as patients with primary sclerosing cholangitis, biliary atresia or other intestinal disorders for whom upper or lower endoscopy is indicated for routine medical management. There may be some participants who are over 18 years of age although the vast majority will be under 18. Vancomycin therapy will be administered to the BA patients (4 weeks)and PSC patients. The PSC patient blood tests would now be done at various intervals: before starting the Vancomycin; every month until their Liver Function Tests are normalized; after their Liver Function Tests are normalized; before stopping the Vancomycin and after they are off the Vancomycin at month 1,3,6,12,and 24. Fecal samples will be taken.

In addition, patients who will already be undergoing either upper or lower intestinal endoscopy for routine diagnostic or therapeutic purposes will be asked to agree to endoscopic mucosal brushings in addition to mucosal biopsies. Some will be patients with a diagnosis of primary sclerosing cholangitis, biliary atresia, or other intestinal disorders for whom upper or lower endoscopy is indicated for routine medical management. Others will have lower intestinal findings (polyps) or complaints (e.g. occult blood in stool), or upper intestinal findings (dyspepsia, reflux), and will be undergoing lower endoscopy (colonoscopy) or upper endoscopy for routine medical management. Up to 2 biopsies will be obtained from the gastric mucosa and of as many as 6 intestinal sites from each patient. In addition the following brushings will be taken: 2 from mid-esophagus, 2 from lesser curvature of the stomach, 2 from the second portion of the duodenum near the ampulla. 2 from the jejunum 5 cm from the Ligament of Trietz, and 2 from the ileum 10 cm from the ileocecal valve. We will also obtain brushing from the tongue. A sample of saliva will be taken.

Fecal specimens will also be collected just prior to bowel preparation for endoscopy/colonoscopy. If the BA patient is already having a Kasai portoenterostomy, done to remove the diseased bile ducts, we would like to take a biopsy of the bile duct. If the patient has a liver biopsy clinically done we would like to keep a 2mm section of it. If the patient has an intraoperative cholangiogram to evaluate the bile ducts we will collect 2.5 cc. of bile fluid. With regards to the controls, who have other intestinal disorders and are also having clinical endoscopies done, we would request a midesophagus biopsy; a biopsy from the antrum and 2 biopsies from the 4th portion of the duodenum. Cell brushings will be taken from the following areas: 2 from mid-esophagus, 2 from lesser curvature of the stomach, 2 from the second portion of the duodenum near the ampulla. 2 from the jejunum 5 cm from the Ligament of Trietz, and 2 from the ileum 10 cm from the ileocecal valve. We will also obtain brushing from the tongue. A sample of saliva will be taken. If the patient is having a colonoscopy done as part of their clinical care we would request a biopsy from the ileum, cecum, and transverse descending rectum. We would also ask for a saliva sample.

The blood tests would now be done at various intervals: before starting the Vancomycin; every month until their Liver Funtion Tests are normalized; after their Liver Function Tests are normalized; before stopping the Vancomycin and after they are off the Vancomycin at month 1,3,6,12 and 24.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Primary Sclerosing Cholangitis
• Biliary Atresia

Intervention

Drug: Vancomycin

Oral 50mg/Kg per day up to maximum of 1500 mg a day for three months.

Other Name: Vancocin

Study Arms

Experimental: Oral Vancomycin

Vancocin

Intervention: Drug: Vancomycin

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 5, 2016): 32
• Original Actual Enrollment (submitted: March 23, 2011): 21
• Actual Study Completion Date: January 2012
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Clinical diagnosis of biliary atresia or primary sclerosing cholangitis.
• Clinical controls who are undergoing upper endoscopy or colonoscopy and do not have biliary atresia or primary sclerosing cholangitis.
• Subjects who have been on oral vancomycin for 1 year for biliary atresia or -

Exclusion Criteria:

• Patients that have taken antibiotics within the last 3 month will be excluded as this will alter the original bacterial flora.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month to 20 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT01322386
• Other Study ID Numbers: 4751
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Kenneth L. Cox, Stanford University
• Study Sponsor: Stanford University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kenneth L Cox, MD; Stanford University

• PRS Account: Stanford University
• Verification Date: April 2016