Gastrointestinal Microbiota in Primary Sclerosing Cholangitis and Biliary Atresia With Vancomycin
Condition: Primary Sclerosing Cholangitis; Biliary Atresia
MeSH terms: Cholangitis; Cholangitis, Sclerosing; Biliary Atresia
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Vancomycin
Intervention type(s): Drug
Intervention description(s): Oral 50mg/Kg per day up to maximum of 1500 mg a day for three months.
Other intervention name(s): Vancocin
Intervention MeSH terms: Vancomycin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: PSC; BA