Clinical trial NCT05165446: Novel MRE Technique to Assess a Risk Factor for Liver Cancer
Official title: Novel MRE Technique to Assess Tissue Viscoelasticity as a Risk Factor for Liver Cancer
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: NASH - Nonalcoholic Steatohepatitis
Keywords: Fatty Liver
NAFLD
Liver Fibrosis
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2021-12-21
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Novel MRE technique to assess tissue viscoelasticity as a risk factor for liver cancer
timeFrame: For individual patients: duration of the study 8 weeks (including lab, scheduling the MR and 4w post MR period).
Secondary outcomes:
measure: Studies on liver injury and glycemic control.
timeFrame: For individual patients: duration of the study 8 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Hospital
state: California
Study officials:
affiliation: Stanford University
name: Natalie Torok, MD
role: PRINCIPAL_INVESTIGATOR
References: