Evaluation of Non-Invasive Tests for Metabolic Liver Disease

NCT07122700 | Recruiting

• 1 other identifier: NIMBLE Study 2.0
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 4

Brief Summary

The Non-Invasive Biomarkers for Metabolic Liver Disease (NIMBLE) study is a comprehensive, multi-year collaborative effort to standardize, validate and advance the regulatory qualification of blood- and imaging-based biomarkers to diagnose and stage Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH). MASH is characterized by liver inflammation accompanied by simultaneous fat accumulation in the liver.

Conditions

Metabolic Associated Fatty Liver Disease; Metabolic Associated Steatotic Liver Disease; Cirrhosis, Liver; NASH; Liver Fibrosis; Liver Fat; Liver Steatoses; Liver Inflammation

Outcome Measures

Primary Outcomes (5)

• Detection of At-Risk MASH

  Evaluate the diagnostic performance of individual and combined biomarkers (e.g., NIS2+, ADAPT \[PRO-C3-based score\], MRI-AST (MAST) \[MRE + PDFF + AST\], FAST and Metabolomics-Advanced Steatohepatitis Fibrosis (MASEF) \[included in the OWLiver Test\]) for identifying at-risk MASH (MASH + MAS ≥4 + fibrosis stage ≥2).

  within 120 days of study enrollment.

• Fibrosis Staging

  Assess blood-based, imaging, and composite biomarkers (e.g., Enhanced Liver Fibrosis (ELF) Test, Liver Stiffness Measure (LSM) by VCTE, MRE, Agile 3+, Agile 4) for detecting clinically significant fibrosis (≥2), advanced fibrosis (≥3), and fibrosis stage 4 (cirrhosis, histologically defined).

  within 120 days of study enrollment.

• Liver Fat Content Monitoring

  Evaluate imaging-based biomarkers (e.g., MRI-PDFF, Hepatorenal Index, Controlled Attenuation Parameter (CAP)) for hepatic steatosis monitoring.

  within 120 days of study enrollment.

• Diagnostic Enrichment

  Identify biomarkers that enhance participant selection for clinical trials, focusing on populations with at-risk MASH, specific fibrosis stages, or steatosis.

  within 120 days of study enrollment.

• Exploratory Biomarkers

  Investigate exploratory biomarkers (e.g., AI-based histological scoring, sequential testing strategies) for novel diagnostic workflows.

  within 120 days of study enrollment.

Secondary Outcomes (4)

• Comparison to Fibrosis (FIB)-4 or other fibrosis-related standards

  within 120 days of study enrollment.

• Comparison to ALT or other activity-related standards.

  within 120 days of study enrollment.

• Comparison to Histology.

  within 120 days of study enrollment.

• AI-driven histology endpoints

  within 120 days of study enrollment.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will enroll participants with suspected or confirmed diagnosis of MASLD. Sex: Male and female participants Age: ≥ 18 and \< 75 years Population sample: Patients with a high probability of MASLD based on eligibility criteria (details under inclusion/exclusion criteria in Section 5.1) General health status: Patients with suspected or confirmed diagnosis of MASLD and no contraindications precluding participation in any study procedures. Geographic location: United States, multi-site

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged \> 18 years and \< 75 years
• Participants must exhibit some manifestations of metabolic dysregulation. Either:
• A. Physician-diagnosed T2DM for at least 90 days with HbA1c \> 6.5 and antidiabetic therapy, if any, stable for at least 90 days prior to screening or B. At least any one of the following six metabolic syndrome criteria \[6\]
• \. body mass index (BMI) of \> 25 kg/m2 2. waist circumference: i. \> 102 cm for men ii. \> 88.9 cm for women 3. fasting triglyceride concentration \> 150 mg/dL i. or ongoing treatment with triglyceride lowering medication 4. HDL-cholesterol concentration: i. \< 40 mg/dL for men ii. \< 50 mg/dL for women iii. or ongoing treatment with cholesterol lowering medication. 5. fasting glucose concentration \> 100 mg/dL 6. either semi-recumbent or supine blood pressure systolic \> 130 mmHg and/ or diastolic \> 85 mmHg i. or ongoing treatment with antihypertensive medication. 5. FIB-4 \> 1.3 (age \< 65 years) and \> 2.0 (age \> 65 years) 6. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration

You may not qualify if:

• Known history or evidence of other forms of chronic liver disease other than MASLD/MASH including but not limited to viral hepatitis B or C, autoimmune liver disease, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease, hemochromatosis, drug-induced liver disease, conditions involving bile duct obstructions, liver cancer, past history of HCC or HCC treatment, listed for or history of liver transplantation, prior resection of liver, etc.
• Current or past evidence of decompensated liver disease defined by overt ascites that is clinically obvious and requires diuretic therapy, overt encephalopathy requiring therapy or history of variceal hemorrhage
• Circulating Alanine aminotransferase (ALT)\> 5xULN
• Ongoing or recent (within the last two years prior to screening) consumption of significantly greater than moderate amounts of alcohol.
• A standard alcoholic drink is any drink that contains about 14 g of pure alcohol, such as 12 fluid ounces of regular beer 8-10 fluid ounces of malt liquor or flavored malt beverages such as hard seltzer 5 fluid ounces of table wine 3-4 fluid ounces of fortified wine such as sherry or port 2-3 fluid ounces of cordial liqueur or aperitif 1.5 fluid ounces (a single jigger or shot) of brandy, cognac, or distilled spirits such as gin, rum, tequila, vodka, whiskey, etc.
• Significantly greater than moderate alcohol consumption is defined as on average over a 2-year period prior to screening:
• Women
• \>1 standard drink per day and/or
• \>14 standard drinks per week Men
• \>2 standard drinks per day and/or
• \>21 standard drinks per week in men
• An Alcohol Use Disorders Identification Test (AUDIT) score of 7 or higher
• A PEth test score of ≥ 20ng/ml.
• In the opinion of the investigator, any contraindications to liver biopsy including but not limited to having significant uncorrected coagulopathy or thrombocytopenia, on chronic anticoagulation with Direct Oral Anticoagulants (DOACs), or on low dose heparin or Warfarin.
• Uncontrolled systolic blood pressure \> 180 mmHg and diastolic blood pressure \> 120 mmHg at screening. Blood pressure will be obtained after at least 10 minutes of resting in a semi-recumbent or supine position.

Sponsors & Collaborators

• Foundation for the National Institutes of Health: lead

Study Sites (4)

Clinical Pharmacology of Miami

Miami, Florida, 33172, United States

RECRUITING

Ohio Clinical Trials

Columbus, Ohio, 43212, United States

RECRUITING

First Surgical Hospital

Bellaire, Texas, 77401, United States

RECRUITING

Endeavor Clinical Trials

San Antonio, Texas, 78240, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples are collected for biomarker analyses, and liver biopsies are obtained.

MeSH Terms

Conditions

Liver Cirrhosis; Fatty Liver; Hepatitis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Arun Sanyal

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Geraldine Dacpano

CONTACT

908-650-1353; gdacpano@ergclinical.com

Clay Dehn

CONTACT

908-484-4110; cdehn@ergclinical.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2025
• First Posted: August 14, 2025
• Study Start: May 13, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made publicly available upon closeout (estimated Q4 2026). Until that point, all data are governed by the ancillary studies policy.
• Access Criteria: Companies only get access to data they generated and associated clinical values, unless requested via ancillary studies protocol. Project team members who funded the project get access to all IPD.

Locations

US (4)