Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients

NCT02477462 | Completed DMC

• 1 other identifier: 703097
• Study Type: observational
• Target: 124
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Biliary Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Phenotypic Analysis

  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.

  2 years

Secondary Outcomes (2)

• Liver Imaging Analysis

  2 years

• Phlebotomy Injuries

  2 years

Study Arms (2)

Primary Biliary Cirrhosis

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

Other: Clinic visit

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

Interventions

Clinic visit OTHER

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

Primary Biliary Cirrhosis

Baseline visit OTHER

Blood draw and quality of life surveys

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Confirmed PBC diagnosis

You may qualify if:

• 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
• years of age and older.

You may not qualify if:

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

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimens will include serum, plasma, DNA, and RNA. In 20 subjects liver biopsies will be performed and retained.

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

Ambulatory Care

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Christopher L Bowlus, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 22, 2015
• Study Start: May 1, 2015
• Primary Completion: June 6, 2019
• Study Completion: June 6, 2019
• Last Updated: June 11, 2019

Record last verified: 2019-06

Locations

US (1)