Clinical trial NCT05081427: Non-invasive Biomarkers of Metabolic Liver Disease (NIMBLE) Study 1.2
Official title: Non-invasive Biomarkers of Metabolic Liver Disease (NIMBLE); An FNIH Biomarkers Consortium Study: Study 1.2
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Nonalcoholic Fatty Liver
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Foundation for the National Institutes of Health
First posted: 2021-10-18
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: This prospective cross-sectional study will enroll subjects 18 years or older with suspected or confirmed diagnosis of NAFLD. Based on protocol-specified FIB-4 values, about one-third are expected to have low, one-third to have intermediate, and one-third to have high likelihood of advanced fibrosis.

The study will use an interim analysis, adaptive MRI protocol, and adaptive sample size. It is anticipated that up to a total of 48 subjects will be enrolled and complete imaging protocols.

General health status: Patients with suspected or confirmed diagnosis of NAFLD and no contraindications for an MRI exam.

Geographic location: Rochester, Minnesota

Brief summary: This study is a prospective, observational, single-center, short-term cross-sectional study to assess the repeatability and reproducibility of a set of specified MRI quantitative biomarkers.

Detailed description: NIMBLE is a comprehensive, five-year collaborative effort to standardize, compare, validate, and advance the regulatory qualification of imaging and circulating biomarkers to diagnose and stage nonalcoholic steatohepatitis (NASH), and to predict and assess response to therapeutic intervention (https://fnih.org/what-we-do/biomarkers-consortium/programs/nimble).

The purpose of this study is to assess the repeatability and reproducibility of a set of specified MRI quantitative biomarkers. The imaging biomarkers will cover an array of methods that could be applicable to non-alcoholic fatty liver disease (NAFLD), including liver fat, liver stiffness, corrected T1 relaxation time and body composition assessments. The data collected will be used to inform a decision of which of these biomarkers has sufficient precision to be advanced to NIMBLE Stage 2.

Eligibility criteria: Inclusion Criteria:

* Adult (age ≥ 18 years).
* Known or suspected NAFLD based on:
* Prior biopsy ≤ 36 months consistent with NAFLD; OR
* Clinical and laboratory data ≤ 3 months before enrollment consistent with NAFLD: abnormal ALT (\>30 U/L for men, \> 19 U/L for women) without other common causes such as HCV, HBV AND meets criteria or ATP III criteria (2005 revision) for metabolic syndrome with any 3 of the 5:

  i. Waist circumference (WC) \> 102 cm (M) or \> 88 cm (F) ii. Fasting glucose ≥ 100 mg/dL or Rx iii. TG ≥ 150 mg/dL or Rx iv. Elevated blood pressure (SBP ≥ 130 mmHg or DBP ≥ 85 mmHg) v. Reduced HDL-C \< 40 mg/dL (M) or \< 50 gm/dL (W)
* Able and willing to participate, including maintaining steady-state: diet, physical activity, alcohol use, medications.
* Classifiable into one of the following enrollment categories by FIB-4 (ALT, AST, platelets, date of birth) collected at screening visit if not available already within 3 months prior:
* Low likelihood of advanced fibrosis: FIB-4 ≤ 1.3 (about one-third of enrolled subjects, minimum 20%, maximum 45%);
* Intermediate likelihood of advanced fibrosis: 1.3 \< FIB-4 \< 2.67 (about one-third of enrolled subjects, minimum 20%, maximum 45%);
* High likelihood of advanced fibrosis: FIB-4 ≥ 2.67: (about one-third of enrolled subjects, minimum 20%, maximum 45%).

Exclusion Criteria:

1. Liver disease other than NAFLD
2. Excess alcohol consumption (≥ 2 units/day for women and ≥ 3 units/day for men)
3. Current diagnosis of drug induced liver injury
4. Receiving drug or placebo in treatment trial now or within 30 days
5. Weight loss or gain of ≥ 5 kg in prior 3 months
6. Other factors that in the judgment of the PI might preclude study completion
7. Women who state they are pregnant. Women who state they are pregnant will be excluded in an abundance of caution, since pregnancy might increase intra-abdominal pressure which in turn might affect the assessment of the different-day reproducibility coefficient of MRI and VCTE measurements.
8. Patients with active implants such as pacemakers or defibrillators or any other contraindication to MRI or VCTE scanning.

Primary outcomes:
measure: Reproducibility of liver stiffness
timeFrame: Within 7 days
measure: Reproducibility of liver fat content
timeFrame: Within 7 days
measure: Reproducibility of visceral adipose tissue volume
timeFrame: Within 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Sudhakar Venkatesh, MD
role: PRINCIPAL_INVESTIGATOR
References: