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

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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:
Information provided by (Responsible Party):
Kenneth L. Cox, Stanford University

Tracking Information
First Submitted Date  ICMJE February 10, 2011
First Posted Date  ICMJE March 24, 2011
Results First Submitted Date  ICMJE May 22, 2015
Results First Posted Date  ICMJE March 4, 2016
Last Update Posted Date May 18, 2016
Study Start Date  ICMJE May 2007
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gastrointestinal Microbiota in Primary Sclerosing Cholangitis and Biliary Atresia With Vancomycin
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Sclerosing Cholangitis
  • Biliary Atresia
Intervention  ICMJE Drug: Vancomycin
Oral 50mg/Kg per day up to maximum of 1500 mg a day for three months.
Other Name: Vancocin
Study Arms  ICMJE 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 5, 2016)
32
Original Actual Enrollment  ICMJE
 (submitted: March 23, 2011)
21
Actual Study Completion Date  ICMJE January 2012
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Month to 20 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01322386
Other Study ID Numbers  ICMJE 4751
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kenneth L. Cox, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kenneth L Cox, MD Stanford University
PRS Account Stanford University
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP