Non-Alcoholic Fatty Liver DiseaseNCT04579874
Clinical Performance of LIVERFASt Test Compared w/ Liver Biopsy in Patients w/ NAFLD.
A study testing LIVERFASt in people with Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis, run by Fibronostics USA, Inc at 8 sites in United States.
Trial summary
The primary objective of this study is to assess the clinical performance of LIVERFAStTM In Vitro Diagnostic (IVD) Tests (Fibrosis score, Activity score and Steatosis score) in NAFLD suspected patients for staging of fibrosis and for grading of inflammatory activity and steatosis, taking as reference the liver biopsy… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steatohepatitis, Liver Fibroses
- What is being tested?
- LIVERFASt
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 241 participants
- Where
- 8 sitesUnited States
- Study dates
- 7 Jan 2021to 15 Apr 2022
- Phase
- Interventional
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • Consenting patients with suspected NAFLD (by any means) having had undergone liver biopsy as part as their routine management, simultaneously or within six months from the day of blood sampling for LIVERFAStTM test.
- Aged 18 to 80 years old, inclusive
- Male or Female from any ethnicity
- Willing to undergo blood sampling for LIVERFAStTM testing after 6 to 12 hours fasting
- Willing to allow histological lecture by a pathologist for NASH-CRN and SAF scoring systems analysis of the liver biopsy
- Willing and able to allow access to requested data and who were informed and signed the consent form.
Who cannot join
- • Inability to provide informed consent
- Patients who may be uncooperative with the sample collection procedures
- History of known Severe coagulopathy
- History of known Hepatic abscess
- Renal failure undergoing dialysis (GFR<45)
- History of Malignancy in the past 2 years
Show all 33Show fewer
- Previous liver transplantation
- Suffering with a terminal illness or any other conditions or diseases that the investigator considers inappropriate for study participation
- Secondary causes of hepatic fat accumulation such as significant alcohol consumption, long-term use of a steatogenic medication, ()
- Ongoing or recent significant alcohol consumption defined as >21 standard drinks on average per week in men and >14 standard drinks on average per week in women.8 Approximately 10 g of alcohol equals one 'drink' unit. One unit equals 1 ounce of distilled spirits, one 12-oz beer, or one 4-oz glass of wine.
- Total parenteral nutrition within 3 months of interview
- Short bowel syndrome
- History of gastric or jejunoileal bypass preceding the diagnosis of NAFLD. Bariatric surgery performed concomitant with or following the diagnosis of NAFLD does not exclude enrollment of patients.
- History of biliopancreatic diversion
- Evidence of advanced liver disease defined as a Child-Pugh-Turcotte score of equal to or greater than 10
- Evidence of chronic hepatitis B as marked by the presence of HBsAg in serum (patients with isolated antibody to hepatitis B core antigen, anti-HBc, are not excluded)
- Evidence of chronic hepatitis C as marked by the presence of anti-HCV and HCV RNA in serum; patients with anti-HCV with PCR negative should not be excluded
- Low alpha-1-antitrypsin level and ZZ phenotype (both determined at the discretion of the investigator)
- History of Wilson's disease
- Known glycogen storage disease
- Known dysbetalipoproteinemia
- Known phenotypic hemochromatosis (determined at the discretion of the investigator)
- History of primary biliary cholangitis (PBC)/primary biliary sclerosis (PSC)
- Hepatic vascular lesions (determined at the discretion of the investigator)
- History of liver liver granulomas sarcoidosis, and infectious diseases such as tuberculosis)
- Congenital hepatic fibrosis, polycystic liver disease
- Other metabolic/congenital liver disease
- Evidence of systemic infectious disease
- Known HIV positive
- Disseminated or advanced extrahepatic malignancy
- Conditions that could interfere with LIVERFASt parameters and could lead to risk of false positive/ false negative results:
- Drug induced liver-injury (DILI), acute alcoholic hepatitis
- Acute inflammatory syndrome or sepsis Active drug use or dependence that, in the opinion of the study investigator, would interfere with adherence to study requirements
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
GCGA Physicians, LLC
Cincinnati, Ohio, 45249
Methodist Health System Clinical Research Institute
Dallas, Texas, 75203
Henry Ford Health System
Detroit, Michigan, 48202
Baylor College of Medicine
Houston, Texas, 77030
Houston Methodist Research Institute
Houston, Texas, 77030
Liver Associates of Texas, P.A.
Houston, Texas, 77030
Northwell Health, Inc
Manhasset, New York, 11030
St. Louis University
St Louis, Missouri, 63103
About this study
Official title: Clinical Performance Evaluation of LIVERFASt Tests to Determine Fibrosis Staging, Inflammatory Activity and Steatosis Grading Compared w/ Liver Biopsy in Patients w/ Metabolic Factors & Presumed Non-Alcoholic Fatty Liver Disease (NAFLD).
The primary objective of this study is to assess the clinical performance of LIVERFAStTM In Vitro Diagnostic (IVD) Tests (Fibrosis score, Activity score and Steatosis score) in NAFLD suspected patients for staging of fibrosis and for grading of inflammatory activity and steatosis, taking as reference the liver biopsy with histological classification of the elementary lesions determined according to SAF scores (Bedossa P., Hepatology 2012).
The secondary objective is to assess the performance of LIVERFAStTM for the histological definition of NAFLD, including NAFL and NASH and severe NASH
Read the detailed description
Chronic liver diseases (CLDs), such as chronic viral hepatitis, nonalcoholic fatty liver diseases (NAFLD) and nonalcoholic steatohepatitis (NASH), are a leading cause of morbidity and mortality globally and usually develops over many years. The prevalence of NAFLD has increased in recent years (15% in 2005 to 25% in 2010) mainly due to the increase prevalence of obesity and diabetes. As, approximately 20% of NAFLD cases develop NASH, the associated increase in NASH during the same period is to be expected (33% in 2005 to 59.1% in 2010).
As a result, staging of liver fibrosis is essential in determining the prognosis and optimal treatment for patients with NASH. Furthermore, evaluation of fibrosis in NAFLD patients can help refine treatment options designed to prevent the progression to NASH.
One recent study demonstrates significant sampling variability of routine liver biopsy in patients with NAFLD (Ratziu V. et al. Gastroenterology 2008). The diagnosis of NASH would have been missed in 35% and the discordance for steatosis grading was encountered in 22% of patients.
Developing safe and easily accessible noninvasive modalities to accurately evaluate fibrosis stage of NAFLD and NASH is of utmost importance in clinical practice.
Fibronostics breaks through the burden to serve patients. By empowering their providers with IVD clinical tools within the clinic, the ability to ensure screening and clinical adherence is assured, and the ease for early detection profoundly shifts the $2B economic burden.
LIVERFASt is a non-invasive clinical and staging In-Vitro-Diagnostic (IVD) tool, which has been developed as an alternative to liver biopsy. LIVERFASt is a safe, and reproducible tool which provides surrogate grading and staging of the three elementary features of NASH: steatosis, inflammatory activity and fibrosis.
LIVERFAStTM combines age, gender, weight and height with common liver function tests (ALT, AST, GGT, total bilirubin), lipid profile (total cholesterol, triglycerides), fasting glucose and three specific proteins of the liver with hepatoprotective functions and predictive value in NAFLD -alpha2-macroglobulin (A2M), haptoglobin (HAP) and apolipoprotein A1 (APOA1).
The main aim of this study is to evaluate the clinical value of LIVERFAStTM as a non-invasive biopsy-proven surrogate assessment of non-alcoholic fatty liver disease.
This is a cohort cross-sectional prospective, multi-centre study of an algorithm-based assessment of liver fibrosis, inflammatory activity (steatohepatitis) and steatosis compared to the histological assessment provided by liver biopsy performed in patients with suspected non-alcoholic steatohepatitis (NASH).
- Conditions
- Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steatohepatitis, Liver Fibroses, Liver Inflammation, Liver Steatoses
- Being tested
- LIVERFASt
- Keywords
- LIVERFASt, Liver biopsy, Liver Fibrosis, Liver Activity, Liver Steatosis, Non-invasive serum biomarker, Neural Network, Artificial Intelligence Machine Learning, Algorithm based test
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Liver Cirrhosis, Hepatitis, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LIVERFAStDiagnostic test
blood draw
| Study group | Role | What they receive |
|---|---|---|
| LIVERFASt validation | Experimental | blood draw for LIVERFASt Receives: Diagnostic Test: LIVERFASt |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical performance of LIVERFASt Tests to determine liver fibrosis scores and staging compared with Liver Biopsy in patients with presumed Non-Alcoholic Fatty Liver Disease (NAFLD).
Primary:
Clinical performance of the LIVERFASt Fibrosis score using the results of five serum biomarkers (A2M, Haptoglobin, ApoA1, Total Bilrubin and GGT) for the over-all diagnostic of liver fibrosis (F0, F1, F2, F3 and F4 stages) using Binary and Non-Binary-Area Under the ROC curve
Measured: 12 months
Clinical performance of LIVERFASt Tests to determine inflammatory activity scores and staging compared with Liver Biopsy in patients with presumed Non-Alcoholic Fatty Liver Disease (NAFLD).
Clinical performance of the LIVERFASt Activity scores using the results of six serum biomarkers (A2M, Haptoglobin, ApoA1, Total Bilrubin, GGT and ALT) for the over-all diagnostic of inflammatory activity (A0, A1, A2, A3 and A4 grades) using Binary and Non-Binary-Area Under the ROC curve
Measured: 12 months
Clinical performance of LIVERFAStTM Tests to determine steatosis grading compared with Liver Biopsy in patients with presumed Non-Alcoholic Fatty Liver Disease (NAFLD).
Clinical performance of the LIVERFAstTM Steatosis grading tests using the results of ten serum biomarkers (A2M, Haptoglobin, ApoA1, Total Bilrubin, GGT, ALT, AST, Triglyceride, Cholesterol and Fasting Blood Glucose) for the over-all diagnostic of steatosis (S0, S1, S2 and S3), using Binary and Non-Binary-Area Under the ROC curve
Measured: 12 months
Secondary outcomes (1)
Clinical performance evaluation of the LIVERFASt Tests to evaluate and measure the definition of NAFLD based on fibrosis staging (F0, F1, F2, F3 and F4), inflammatory activity (A0, A1, A2, A3 and A4) and steatosis grading (S0, S1, S2, and S3).
Secondary
200 adult men and women who are between the ages of 18-80 years old patients who have undergone liver biopsy with suspected non-alcoholic fatty liver disease within six (6) months of the enrollment and have undergone blood sampling for LIVERFASt testing using the generated results of ten serum biomarkers, namely: A2M, Haptoglobin, ApoA1, Total Bilrubin, GGT, ALT, AST, Triglyceride, Cholesterol and Fasting Blood Glucose, for the over-all diagnosis of fibrosis (F0, F1 to F4), activity (A0, A1 to A4) and steatosis (S0, S1 to S3). Performance (Bin-AUROC) of the LIVERFASt using the results of the combination of the ten biomarkers for the NAFLD definitions of NAFL, NASH and significant NASH (>S1≥A2≥F2)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start7 Jan 2021
- Primary completion15 Dec 2021
- Study completion15 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fibronostics USA, Inc
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ronald Quiambao, MD, Study director, Fibronostics USA, IncImtiaz Alam, MD, Principal investigator, Ohio Gastroenterology and Liver InstituteSven Henrichwark, Study chair, Fibronostics USA, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04579874
- Sponsor's protocol ID
- Fibro-US-001-0200
- Status last verified
- Jul 2022
- First submitted
- 25 Sep 2020
- Last updated
- 2 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Performance Evaluation of LIVERFASt Tests to Determine Fibrosis Staging, Inflammatory Activity and Steatosis Grading Compared w/ Liver Biopsy in Patients w/ Metabolic Factors & Presumed Non-Alcoholic Fatty Liver Disease (NAFLD).
- ClinicalTrials.gov ID
- NCT04579874
- Acronym / sponsor ID
- Fibro-US-001-0200
- Conditions
- Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steatohepatitis, Liver Fibroses, Liver Inflammation, Liver Steatoses
- Keywords
- LIVERFASt, Liver biopsy, Liver Fibrosis, Liver Activity, Liver Steatosis, Non-invasive serum biomarker, Neural Network, Artificial Intelligence Machine Learning
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Fibronostics USA, IncUniversity, hospital or other
- Study start
- 7 Jan 2021 (actual)
- Primary completion
- 15 Dec 2021 (actual)
- Study completion
- 15 Apr 2022 (actual)
- First posted
- 8 Oct 2020 (actual)
- 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.
The primary objective of this study is to assess the clinical performance of LIVERFAStTM In Vitro Diagnostic (IVD) Tests (Fibrosis score, Activity score and Steatosis score) in NAFLD suspected patients for staging of fibrosis and for grading of inflammatory activity and steatosis, taking as reference the liver biopsy with histological classification of the elementary lesions determined according to SAF scores (Bedossa P., Hepatology 2012).
The secondary objective is to assess the performance of LIVERFAStTM for the histological definition of NAFLD, including NAFL and NASH and severe NASH
Detailed description
Chronic liver diseases (CLDs), such as chronic viral hepatitis, nonalcoholic fatty liver diseases (NAFLD) and nonalcoholic steatohepatitis (NASH), are a leading cause of morbidity and mortality globally and usually develops over many years. The prevalence of NAFLD has increased in recent years (15% in 2005 to 25% in 2010) mainly due to the increase prevalence of obesity and diabetes. As, approximately 20% of NAFLD cases develop NASH, the associated increase in NASH during the same period is to be expected (33% in 2005 to 59.1% in 2010).
As a result, staging of liver fibrosis is essential in determining the prognosis and optimal treatment for patients with NASH. Furthermore, evaluation of fibrosis in NAFLD patients can help refine treatment options designed to prevent the progression to NASH.
One recent study demonstrates significant sampling variability of routine liver biopsy in patients with NAFLD (Ratziu V. et al. Gastroenterology 2008). The diagnosis of NASH would have been missed in 35% and the discordance for steatosis grading was encountered in 22% of patients.
Developing safe and easily accessible noninvasive modalities to accurately evaluate fibrosis stage of NAFLD and NASH is of utmost importance in clinical practice.
Fibronostics breaks through the burden to serve patients. By empowering their providers with IVD clinical tools within the clinic, the ability to ensure screening and clinical adherence is assured, and the ease for early detection profoundly shifts the $2B economic burden.
LIVERFASt is a non-invasive clinical and staging In-Vitro-Diagnostic (IVD) tool, which has been developed as an alternative to liver biopsy. LIVERFASt is a safe, and reproducible tool which provides surrogate grading and staging of the three elementary features of NASH: steatosis, inflammatory activity and fibrosis.
LIVERFAStTM combines age, gender, weight and height with common liver function tests (ALT, AST, GGT, total bilirubin), lipid profile (total cholesterol, triglycerides), fasting glucose and three specific proteins of the liver with hepatoprotective functions and predictive value in NAFLD -alpha2-macroglobulin (A2M), haptoglobin (HAP) and apolipoprotein A1 (APOA1).
The main aim of this study is to evaluate the clinical value of LIVERFAStTM as a non-invasive biopsy-proven surrogate assessment of non-alcoholic fatty liver disease.
This is a cohort cross-sectional prospective, multi-centre study of an algorithm-based assessment of liver fibrosis, inflammatory activity (steatohepatitis) and steatosis compared to the histological assessment provided by liver biopsy performed in patients with suspected non-alcoholic steatohepatitis (NASH).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LIVERFASt validation | Experimental | Diagnostic Test: LIVERFAStblood draw for LIVERFASt |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- • Consenting patients with suspected NAFLD (by any means) having had undergone liver biopsy as part as their routine management, simultaneously or within six months from the day of blood sampling for LIVERFAStTM test.
Key exclusion criteria (33 listed)
- • Inability to provide informed consent
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 |
|---|---|---|
| LIVERFAStblood draw | Diagnostic test | LIVERFASt validation |
Primary outcome
Clinical performance of LIVERFASt Tests to determine liver fibrosis scores and staging compared with Liver Biopsy in patients with presumed Non-Alcoholic Fatty Liver Disease (NAFLD).
Time frame: 12 months
Primary: Clinical performance of the LIVERFASt Fibrosis score using the results of five serum biomarkers (A2M, Haptoglobin, ApoA1, Total Bilrubin and GGT) for the over-all diagnostic of liver fibrosis (F0, F1, F2, F3 and F4 stages) using Binary and Non-Binary-Area Under the ROC curve
Clinical performance of LIVERFASt Tests to determine inflammatory activity scores and staging compared with Liver Biopsy in patients with presumed Non-Alcoholic Fatty Liver Disease (NAFLD).
Time frame: 12 months
Clinical performance of the LIVERFASt Activity scores using the results of six serum biomarkers (A2M, Haptoglobin, ApoA1, Total Bilrubin, GGT and ALT) for the over-all diagnostic of inflammatory activity (A0, A1, A2, A3 and A4 grades) using Binary and Non-Binary-Area Under the ROC curve
Clinical performance of LIVERFAStTM Tests to determine steatosis grading compared with Liver Biopsy in patients with presumed Non-Alcoholic Fatty Liver Disease (NAFLD).
Time frame: 12 months
Clinical performance of the LIVERFAstTM Steatosis grading tests using the results of ten serum biomarkers (A2M, Haptoglobin, ApoA1, Total Bilrubin, GGT, ALT, AST, Triglyceride, Cholesterol and Fasting Blood Glucose) for the over-all diagnostic of steatosis (S0, S1, S2 and S3), using Binary and Non-Binary-Area Under the ROC curve
1 secondary outcome
Clinical performance evaluation of the LIVERFASt Tests to evaluate and measure the definition of NAFLD based on fibrosis staging (F0, F1, F2, F3 and F4), inflammatory activity (A0, A1, A2, A3 and A4) and steatosis grading (S0, S1, S2, and S3).
Time frame: 12 months
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 2 Aug 2022.
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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.
Ronald Quiambao, MD study director
Fibronostics USA, Inc
Imtiaz Alam, MD principal investigator
Ohio Gastroenterology and Liver Institute
Sven Henrichwark study chair
Fibronostics USA, Inc
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LIVERFASt in people with Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis, run by Fibronostics USA, Inc at 8 sites 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 6 inclusion and 33 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 2 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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?
Clinical performance of LIVERFASt Tests to determine liver fibrosis scores and staging compared with Liver Biopsy in patients with presumed Non-Alcoholic Fatty Liver Disease (NAFLD). (time frame: 12 months). The study lists 3 primary outcomes in all. 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 2 Aug 2022.