Clinical Trials Logo

Clinical Trial Summary

Nonalcoholic fatty liver disease is the most common liver disease in Western countries, due in large part to its association with type 2 diabetes and obesity. The more advanced form of this disease is known as nonalcoholic steatohepatitis (NASH). If left untreated, NASH can evolve to cirrhosis, the late stage of fibrosis. Once cirrhosis is established, patients are at increased risk of developing gastrointestinal bleeding, liver cancer and liver failure that may require transplantation. A liver biopsy is currently needed to diagnose the severity of fatty liver disease but this is usually not indicated in asymptomatic patients. This procedure requires the insertion of a needle inside the liver to remove a small piece of tissue for examination under microscope. Liver biopsy is an invasive procedure with a small risk of major complications such as bleeding in 0.5% of cases. It is also affected by sub-optimal sampling leading to diagnostic errors Ultrasound is optimum for screening patients with or without symptoms because it is a safe and widely available technology to scan the whole liver. Members of our team have developed Advanced ultrasound techniques that provide unique information not possible with state-of-the-art techniques. Unlike liver biopsy, these techniques would be applicable even in asymptomatic patients because it is non-invasive. This research proposal proposes a novel approach for diagnosis of NASH and will be the first study to measure individual components of NASH (fat, inflammation and fibrosis) with quantitative ultrasound (QUS) scores. This study is timely because NASH is the second leading cause of liver transplantation in North America and is predicted to become the leading indication in the near future.


Clinical Trial Description

BACKGROUND - Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in Western countries. The more advanced form, nonalcoholic steatohepatitis (NASH) may evolve to fibrosis, cirrhosis, liver failure and liver cancer. Liver biopsy is the current reference standard for diagnosis of NASH. However, its invasiveness prevent its use for large-scale screening and diagnosis. Members of our team have developed innovative quantitative ultrasound (QUS) techniques (shear wave viscoelastography and sub-resolution cellular imaging) that have a high diagnostic potential. Advantages over magnetic resonance (MR) include the ability to characterize viscosity, cellular organizations and cost-effectiveness. We hypothesize that a combination of QUS techniques offering complementary assessment of tissue characteristics will differentiate NASH from NAFLD and quantify evolving grades of liver fat, inflammation and fibrosis. OBJECTIVES - Primary objective: 1) Determine the accuracy of QUS parameters for diagnosis of NASH. Secondary objectives: 2) Determine the diagnostic accuracy of QUS for grading histology-determined liver fat, inflammation and fibrosis. 3) Compare the diagnostic accuracy of QUS and MR techniques for liver fat quantification. Hypotheses: We hypothesize that QUS methods, including viscoelasticity, homodyned-K parameters and attenuation parameters can characterize properties of tissues encountered in NASH (including liver fat, inflammation and fibrosis). METHODOLOGY - Design: This will be a cross-sectional imaging trial to evaluate the diagnostic accuracy of QUS techniques in 10 non-obese volunteers and 92 patients, using histopathology as the reference standard for patients. Paired index tests QUS-based (mechanical and cellular parameters) and MR-based (mechanical parameters and relaxation times reflecting tissue content) techniques will be performed as research procedures in close temporal proximity to the reference test (liver biopsy). Inclusion criteria: Consecutive adult patients with known or suspected NAFLD or NASH undergoing a liver biopsy for clinical indications. Exclusion criteria: Contraindication to MR, refusal to participate, any other cause of chronic liver disease or prior liver transplantation. Data analysis: Random forest classifier to develop a predictive model. Cross-validated receiver operating characteristic curve analysis, sensitivity and specificity to assess diagnostic accuracy. RATIONALE AND IMPACT - NASH has become the second leading cause of liver transplantation in North America and is predicted to become the leading indication in the near future. While liver biopsy is the established reference standard for NASH diagnosis and MR constitutes a noninvasive alternative, they are both impractical for large-scale application. Thus, there is an urgent need to investigate non-invasive and cost-effective techniques for diagnosis of NASH. Our proposed QUS techniques are experimental and currently not available on clinical US systems. A major impact of this work, for patients and medical institutions, will be to lower the need for liver biopsy, the risk of complications and reduce the cost for NASH diagnosis while providing quantitative therapeutic targets. ;


Study Design


Related Conditions & MeSH terms

  • Fatty Liver
  • Liver Diseases
  • Non-alcoholic Fatty Liver Disease
  • Nonalcoholic Fatty Liver Disease (NAFLD)
  • Nonalcoholic Steatohepatitis (NASH)

NCT number NCT03572465
Study type Observational
Source Centre hospitalier de l'Université de Montréal (CHUM)
Contact An Tang, MD, MSc
Phone 514-890-8000
Email an.tang@umontreal.ca
Status Recruiting
Phase
Start date October 23, 2019
Completion date October 30, 2024

See also
  Status Clinical Trial Phase
Active, not recruiting NCT04880031 - A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) Phase 2
Suspended NCT04104321 - A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With NASH (ARMOR) Phase 3
Completed NCT02891408 - Study to Evaluate the Pharmacokinetics of Firsocostat or Fenofibrate in Adults With Normal and Impaired Hepatic Function Phase 1
Completed NCT04546984 - Multiple Dose Safety, Tolerability, PK,PD and Food Effect Study of HEC96719 in Healthy Adult Subjects Phase 1
Recruiting NCT05842512 - Study of ADI-PEG 20 Versus Placebo in Subjects With NASH Phase 2
Completed NCT02854605 - Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Participants With Nonalcoholic Steatohepatitis (NASH) Phase 2
Recruiting NCT06108219 - A Phase 2b, Study Evaluating Miricorilant in Adult Patients With Nonalcoholic Steatohepatitis/Metabolic Dysfunction-Associated Steatohepatitis (MONARCH) Phase 2
Active, not recruiting NCT05402371 - A Study to Evaluate the Efficacy and Safety of Rencofilstat in Subjects With NASH and Advanced Liver Fibrosis Phase 2
Terminated NCT03823703 - Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Miricorilant in Participants With Presumed Nonalcoholic Steatohepatitis (NASH) Phase 2
Recruiting NCT05117489 - A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Miricorilant in Patients With Presumed Nonalcoholic Steatohepatitis (NASH) Phase 1
Completed NCT04165343 - Evaluation of Multi-Organ Metabolism and Perfusion in NAFLD by Total Body Dynamic PET Scan on EXPLORER
Recruiting NCT04913090 - A Phase I Clinical Trial of XZP-5610 Tablets in Healthy Subjects Phase 1
Recruiting NCT06024408 - A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor Phase 1
Terminated NCT04004325 - A Study of FT 4101 in Overweight/Obese Participants With Non-alcoholic Steatohepatitis Phase 1/Phase 2
Completed NCT06037577 - Subcutaneous Doses of CM-101 as a Treatment for Medical Conditions Involving Inflammatory and Fibrotic Mechanisms in Healthy Male Subjects Phase 1
Active, not recruiting NCT05320146 - A Sub Study of the Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Miricorilant in Patients With Presumed Nonalcoholic Steatohepatitis (NASH)
Completed NCT01265498 - The Farnesoid X Receptor (FXR) Ligand Obeticholic Acid in NASH Treatment Trial(FLINT) Phase 2
Terminated NCT00845845 - Fish Oil and Diet for the Treatment of Non-Alcoholic Steatohepatitis (NASH) Phase 2
Terminated NCT04267393 - Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH) Phase 2
Completed NCT04616014 - A Study of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients With Nonalcoholic Steatohepatitis (NASH) Phase 2