Clinical trial NCT02477462: Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients
Official title: Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Primary Biliary Cirrhosis
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2015-06-22
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Confirmed PBC diagnosis

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.

Eligibility 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.

Primary outcomes:
measure: Phenotypic Analysis
timeFrame: 2 years
Secondary outcomes:
measure: Liver Imaging Analysis
timeFrame: 2 years
measure: Phlebotomy Injuries
timeFrame: 2 years
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
Study officials:
affiliation: University of California, Davis
name: Christopher L Bowlus, MD
role: PRINCIPAL_INVESTIGATOR
References: