Novel MRE Technique to Assess a Risk Factor for Liver Cancer

Novel MRE Technique to Assess Tissue Viscoelasticity as a Risk Factor for Liver Cancer

The aim of this proposal is to investigate a novel imaging method to identify patients with non-alcoholic steatohepatitis (NASH) who are at risk for hepatocellular carcinoma (HCC).

Study Overview

• Status: Active, not recruiting
• Conditions: NASH - Nonalcoholic Steatohepatitis

Detailed Description

NASH is the most common cause of chronic liver disease, and it is estimated that 40-50% of patients with obesity and T2DM have NASH. NASH can lead to HCC with the risk increasing 2-3 fold in patient with poor glycemic control. Unless caught early, HCC has a poor prognosis with no effective therapies. A unique feature of HCC in NASH is that it often arises at a pre-cirrhotic stage, and the prognosis is often dismal. There are no current surveillance strategies for these pre-cirrhotic patients. Based on our animal models and pilot patient studies, we developed a novel paradigm that linked liver matrix changes to a more aggressive HCC phenotype. Our goal is to develop an imaging-based surveillance tool that will identify early matrix changes that may predispose to HCC.

• Study Type: Observational
• Enrollment (Estimated): 35

Contacts and Locations

• Study Contact: Name: Natalie Torok, MD; Phone Number: 650-498-7878; Email: ntorok@stanford.edu
• Study Contact Backup: Name: Agatha Okobi; Phone Number: 650-498-1264; Email: aokobi@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study will include one group of healthy subjects and two groups with 15 patients each which will enroll in parallel, one group with type 2 diabetes mellitus (T2DM), and one group without DM.

Description

Inclusion Criteria:

1. Male or non-pregnant/non-lactating women ≥ 18 years of age
2. Diagnosis of NASH
3. Diagnosis of pre-cirrhotic fibrosis (F1-F3), diagnosed as per standard of care (history, exam, laboratory tests, Fibroscan, within 6 months of enrollment)
4. Na-MELD < 9: The Na-MELD (sodium-Model for End Stage Liver Disease) score is routinely used to assess liver synthetic function and life expectancy. Patients with Na-MELD<9 have less than 1.9% 3 months liver-related mortality risk, and their liver synthetic function is normal.
5. Groups both with and without T2DM will be enrolled.
6. Women of childbearing potential must agree to at least two methods of contraception.
7. Will not participate in any other clinical trial for the duration of the study
8. Will not consume alcohol for the duration of the study
9. If on vitamin E, pioglitazone or any anti diabetic treatment prior to the study, will have been on stable therapies for 6 months prior to enrolment.
10. Able to undergo 3 Tesla MRI and complete MRI screening form
11. Ability to understand and the willingness to sign a written informed consent document.
12. ECOG or Karnofsky Performance Status will be not be employed

Exclusion Criteria:

1. Presence of any other form of liver disease, including viral hepatitis, autoimmune hepatitis, alcoholic liver disease, genetic causes of chronic liver disease, cardiogenic liver disease, and HIV positivity (can cause liver fibrosis).
2. ALT>300 U/l
3. Total serum bilirubin ≥ to 1.3 mg/dL (Gilbert's Syndrome patients are excepted)
4. International Normalized Ratio (INR) ≥ 1.3
5. MELD>9
6. Serum creatinine >2.0mg/dl

7. Known alcohol abuse or alcohol use disorder (AUDIT profile and/or pos. urine ethylglucuronide):

   • >20 g/day for women
   • >30 g/day for men
8. Active substance abuse
9. Platelet count ≤100//mm3
10. Hemoglobin <11 g/dl in females or <12 g/dl in males
11. Presence/history of HCC, or other primary or metastatic cancer to the liver.
12. History of liver transplantation
13. History of bariatric surgery
14. History of inflammatory bowel disease
15. History of advanced pulmonary disease
16. Any concerns regarding compliance by enrolling physician
17. Pregnant or lactating women.
18. Presence of cardiac implantable electronic device (CIED)
19. History of CIED with retained leads
20. Presence of any metallic foreign body that is unsafe for the MRI environment
21. Inability to undergo MRI based on responses to the MRI screening form
22. History of claustrophobia or the need for sedation to undergo MRI

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Novel MRE technique to assess tissue viscoelasticity as a risk factor for liver cancer	Safety:MRE evaluation of the liver for stiffness is a standard of care test. We do not expect issues as this is a non-invasive technique. Our MR may require a longer session compared to the traditional MRE (40 minutes of scan time for multifrequency MRE, as compared to 25 minutes for conventional MRE). However, all issues, patient symptoms will be recorded. Technical Feasibility: The MRE algorithm we will use has previously been shown to produce data from a different scanner platform, across all frequencies. Feasibility of multifrequency MRE will be assessed by descriptive summary of technical success and image quality for each of the individual reconstructed MRE datasets (stiffness, elasticity, and viscosity). Mean and standard deviation for the MRE outcome variables viscosity elasticity and stiffness will be presented and tested for the difference in means between the 2 groups by way of ANOVA, and if a difference is found, followed by Tukey's test.	For individual patients: duration of the study 8 weeks (including lab, scheduling the MR and 4w post MR period).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Studies on liver injury and glycemic control.	assess correlation to liver injury (AST, ALT) assess correlation to glycemic control HbA1c	For individual patients: duration of the study 8 weeks

Collaborators and Investigators

• Sponsor: Natalie Torok
• Investigators: Principal Investigator: Natalie Torok, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: December 7, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 21, 2021

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: NAFLD; Fatty Liver; Liver Fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Neoplasms
• Other Study ID Numbers: 62249

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No