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Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by University of California, Davis
Sponsor:
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT02477462
First received: June 10, 2015
Last updated: February 13, 2017
Last verified: November 2016
  Purpose

Primary biliary cirrhosis (PBC) is a progressive autoimmune disease of biliary epithelial cells resulting in biliary cirrhosis. PBC is characterized by a 90% female predominance, high titers of serum anti-mitochondrial autoantibodies (AMA) directed against the pyruvate dehydrogenase complex E2 subunit and evidence from both human and murine models suggests that T-cells, particularly cluster of differentiation (CD) 8+ T cells, are key to the destruction of bile ducts. However, clinical trials of classic immunosuppressive drugs including corticosteroids, azathioprine, methotrexate, and tacrolimus have been largely unsuccessful in altering the disease course. This is a single center, prospective, non-treatment study of the role of immune responses in PBC patients.

Non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic steatohepatitis (NASH) are common, often "silent" liver diseases. NASH resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and fibrosis. NASH can be severe and can lead to cirrhosis and hepatocellular carcinoma. Ten to 20 percent of American have NAFLD with NASH affecting 2 to 5 percent of Americans.


Condition Intervention
Primary Biliary Cirrhosis
Other: Clinic visit
Other: Baseline visit

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Phenotypic Analysis [ Time Frame: 2 years ]
    Comparison of PBC phenotypes defined by alkaline phosphatase response to treatment and degree of fibrosis determined by transient elastography. In addition, Principle component analysis (PCA) and non-negative matrix factorization (NMF) will be used to identify phenotypic subject stratification utilizing both cytokine and gene expression data at baseline. The alkaline phosphatase (ALP) will be compared between these classes to determine if there is an association between classes.


Secondary Outcome Measures:
  • Liver Imaging Analysis [ Time Frame: 2 years ]
    Transient elastography (FibroScan) and MR elastography will provide a measurement of liver stiffness. The liver stiffness metrics will be tabulated for each of the three time points and assessed for change.

  • Phlebotomy Injuries [ Time Frame: 2 years ]
    Number of injuries occurring as a result of phlebotomy during the study.


Biospecimen Retention:   Samples With DNA
Biospecimens will include serum, plasma, DNA, and RNA. In 20 subjects liver biopsies will be performed and retained.

Estimated Enrollment: 200
Study Start Date: May 2015
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Primary Biliary Cirrhosis
Subjects meeting internationally accepted criteria for the diagnosis of primary biliary cirrhosis
Other: Clinic visit
Blood draw every 3 months; quality of life surveys and imaging annually
Control
Subjects without evidence of primary biliary cirrhosis, liver disease, or inflammatory condition who are of similar age and sex distribution to the Primary Biliary Cirrhosis group
Other: Baseline visit
Blood draw and quality of life surveys

Detailed Description:
In this study, the investigators will prospectively collect demographic, clinical, and laboratory data and blood samples for research purposes on 45 PBC patients and 50 male and female NAFLD patients. PBC and NAFLD diagnosis and clinical status will be evaluated by magnetic resonance (MR) elastography, transient elastography (FibroScan®) and blood lab analysis including anti-mitochondrial antibodies (AMA), anti-nuclear antibodies (ANA), immunoglobulins, complete blood count (CBC), comprehensive metabolic panel (CMP) and coagulation measures). Additionally serum and blood will be obtained from the patients on the first visit and at months 3, 6, 9, 12, 15, 18, 21 & 24. Serum and blood samples will be used to measure serum cytokine abundance and transcriptome analysis. For comparison, 95 age (+/- 5 years) and sex-matched controls without PBC will be recruited for a clinical laboratory, cytokine, gene expression analysis. Control subjects will have blood drawn at a single time point.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Confirmed PBC diagnosis
Criteria

Inclusion Criteria for Primary Biliary Cirrhosis Group:

  • PBC diagnosis based upon at least 2 of 3 criteria: AMA titer > 1:40; Alkaline phosphatase > 1.5 times the upper limit of normal (ULN) for at least 6 months; and Liver biopsy findings consistent with PBC
  • 18 years of age and older.

Exclusion Criteria:

  • Presence of other concomitant liver diseases including viral hepatitis, primary sclerosing cholangitis (PSC), alcoholic liver disease, Wilson's disease, hemochromatosis, or Gilbert's syndrome.
  • Prior liver transplantation
  • Use of immunosuppressants within 6 months of Day 0, including azathioprine, prednisone, prednisolone, budesonide, cyclosporine, tacrolimus, methotrexate, or mycophenolate mofetil.
  • Use of biologic agents including anti-cell and anti-cytokine therapies within 12 months.

Inclusion Criteria for Control Subjects

  • Absence of liver disease or inflammatory conditions
  • 18 years of age and older.

Exclusion Criteria for Control Subjects

  • Presence of concomitant liver diseases including PBC, viral hepatitis, PSC, alcoholic liver disease, Wilson's disease, hemochromatosis, or Gilbert's syndrome.
  • Prior liver transplantation
  • Use of immunosuppressants within 6 months, including azathioprine, prednisone, prednisolone, budesonide, cyclosporine, tacrolimus, methotrexate, or mycophenolate mofetil.
  • Use of biologic agents including anti-cell and anti-cytokine therapies within 12 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02477462

Contacts
Contact: Christopher L Bowlus, MD 916-734-8985 clbowlus@ucdavis.edu
Contact: Christopher E Bowlus, MD 530-752-2884 clbowlus@ucdavis.edu

Locations
United States, California
University of California Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Sandeep Dhaliwal, MD    916-734-8696    sandhaliwal@ucdavis.edu   
Principal Investigator: Christopher L Bowlus, MD         
Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: Christopher L Bowlus, MD University of California, Davis
  More Information

Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT02477462     History of Changes
Other Study ID Numbers: 703097
Study First Received: June 10, 2015
Last Updated: February 13, 2017

Additional relevant MeSH terms:
Liver Cirrhosis, Biliary
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Liver Cirrhosis

ClinicalTrials.gov processed this record on May 22, 2017