Primary Biliary CirrhosisNCT02477462
Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients
An observational study of Primary Biliary Cirrhosis, run by University of California, Davis at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- Clinic visit and Baseline visit
- How many people
- 124 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to 6 Jun 2019
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Confirmed PBC diagnosis
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Medical Center
Sacramento, California, 95817
About this study
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.
Read the 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
- Being tested
- Clinic visit, Baseline visit
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinic visitOther
Blood draw every 3 months; quality of life surveys and imaging annually
Baseline visitOther
Blood draw and quality of life surveys
| Study group | Role | What they receive |
|---|---|---|
| Primary Biliary Cirrhosis | Subjects meeting internationally accepted criteria for the diagnosis of primary biliary cirrhosis Receives: 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 Receives: Other: Baseline visit |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (2)
Liver Imaging Analysis
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.
Measured: 2 years
Phlebotomy Injuries
Number of injuries occurring as a result of phlebotomy during the study.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2015 (estimated)
- Study startMay 2015
- Primary completion6 Jun 2019
- Study completion6 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 124 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christopher L Bowlus, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02477462
- Sponsor's protocol ID
- 703097
- Status last verified
- Jun 2019
- First submitted
- 10 Jun 2015
- Last updated
- 11 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients
- ClinicalTrials.gov ID
- NCT02477462
- Acronym / sponsor ID
- 703097
- Conditions
- Primary Biliary Cirrhosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- 6 Jun 2019 (actual)
- Study completion
- 6 Jun 2019 (actual)
- First posted
- 22 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Primary Biliary Cirrhosis | – | Other: Clinic visitSubjects meeting internationally accepted criteria for the diagnosis of primary biliary cirrhosis |
| Control | – | Other: Baseline visitSubjects 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Confirmed PBC diagnosis
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinic visitBlood draw every 3 months; quality of life surveys and imaging annually | Other | Primary Biliary Cirrhosis |
| Baseline visitBlood draw and quality of life surveys | Other | Control |
Primary outcome
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.
2 secondary outcomes
Liver Imaging Analysis
Time frame: 2 years
Phlebotomy Injuries
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher L Bowlus, MD principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Biliary Cirrhosis, run by University of California, Davis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phenotypic Analysis (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2019.