Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients

NCT ID: NCT02477462

Last Updated: 2019-06-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 124 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2019-06-06

Brief Summary

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.

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.

Conditions

Primary Biliary Cirrhosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Primary Biliary Cirrhosis

Subjects meeting internationally accepted criteria for the diagnosis of primary biliary cirrhosis

Clinic visit

Intervention Type: OTHER

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

Baseline visit

Intervention Type: OTHER

Blood draw and quality of life surveys

Interventions

Clinic visit

Blood draw every 3 months; quality of life surveys and imaging annually

Intervention Type: OTHER

Baseline visit

Blood draw and quality of life surveys

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

• Absence of liver disease or inflammatory conditions
• 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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher L Bowlus, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California Davis Medical Center

Sacramento, California, United States

Countries

United States

Other Identifiers

703097

Identifier Type: -

Identifier Source: org_study_id