Noninvasive Biomarkers of Metabolic Liver Disease 1.1

NCT04828551 | Completed Results FDA Device

• 1 other identifier: 2019P002092
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

NIMBLE is a comprehensive 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). This study focuses on estimating the repeatability and reproducibility of ultrasound elastography-based biomarkers across a range of fibrosis stages.

Conditions

Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver

Outcome Measures

Primary Outcomes (2)

• Evaluation of Pooled Different-day, Different-operator Reproducibility of Shear Wave Speed Measurements

  The same research subject undergoes multiple shear wave elastography measurements (measured in m/s) on multiple ultrasound imaging devices and transient elastography at two visits (baseline + up to 7 days) with different operators. Elastographic measurements are recorded. The median shear wave velocity value (in m/s) is computed for each ultrasound imaging device and is displayed by the transient elastography device. The ultrasound machine measurements are pooled and the pooled different day-different operator reproducibility coefficient for the group of ultrasound machines is computed. The reproducibility coefficient for transient elastography is computed separately. The pooled different-day, different-operator reproducibility coefficient of ultrasound measurements of shear wave speed, is reported in the outcome measure data table section.

  (2 visits, baseline + up to 7 days). Outcome measure will be assessed after pooling measurements from all study subjects.

• Different-day, Different-operator Reproducibility Coefficient of Transient Elastography Based Shear Wave Speed Measurements

  The same research subject undergoes multiple shear wave elastography measurements (measured in m/s) on multiple ultrasound imaging devices and transient elastography at two visits (baseline + up to 7 days) with different operators. Elastographic measurements are recorded. The median shear wave velocity value (in m/s) is computed for each ultrasound imaging device and is displayed by the transient elastography device. The ultrasound machine measurements are pooled and the pooled different day-different operator reproducibility coefficient for the group of ultrasound machines is computed. The reproducibility coefficient for transient elastography is computed separately. The pooled different-day, different-operator reproducibility coefficient of transient elastography measurements (in m/s unit), is reported in the outcome measure data table section.

  (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects.

Secondary Outcomes (3)

• Evaluation of Pooled Same-day, Same-operator Repeatability of Shear Wave Speed (SWS)

  (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling measurements from all study subjects.

• Evaluation of Pooled Different-scanner, Same-day Reproducibility of Shear Wave Elastography.

  (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects.

• Evaluation of Same-day, Same-operator Repeatability of Transient Elastography

  (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects.

Study Arms (1)

MGH and UCSD Study subjects

OTHER

This study will enroll patients 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. Sex: 50:50 - Note- no stratification will be done based on sex Age: ≥ 18 yrs Demographic group: Patients with a high probability of NAFLD based on the eligibility criteria General health status: Patients with suspected or confirmed diagnosis of NAFLD Geographic location: Boston, MA (greater metropolitan areas) and San Diego, CA (greater metropolitan areas)

Device: Ultrasound based shear wave speed and fat quantification methods; Diagnostic Test: Blood collection; Other: Physical measurements; Other: Clinical history and medication reviews

Interventions

Ultrasound based shear wave speed and fat quantification methods DEVICE

Ultrasound based imaging parameters will be collected from all patients in two visits. These will include but may not be limited to SWE results, Quantitative ultrasound parameters,where available,including Attenuation Coefficient, Backscatter Coefficient, Shear Wave Dispersion, Speed of Sound, Ultrasound derived fat fraction Conventional Bmode (gray-scale) and Doppler ultrasound images,including An image of the liver and right kidney on the same image for hepatorenal index calculation Right liver lobe for skin to liver capsule distance calculation Portal vein Doppler for portal vein pulsatility index measurement VCTE and Controlled Attenuation Parameter measurements with the Fibroscan system

MGH and UCSD Study subjects

Blood collection DIAGNOSTIC_TEST

Blood will be collected by trained phlebotomists at each site using routine methods and standard collection tubes. Total volume is expected to be about 10 mL or less Blood collected at MGH will be analyzed by the MGH clinical laboratory. Blood collected at UCSD will be analyzed by the UCSD clinical laboratory. Blood results obtained within the 3-month interval prior to the screening visit at the MGH or UCSD laboratories will be considered acceptable for study analyses and may be used at PI discretion. For each laboratory, the normal ranges for each blood test will be recorded and filed

MGH and UCSD Study subjects

Physical measurements OTHER

Height will be recorded at Screening. Weight and vital signs will be recorded at each visit. Body mass index will be calculated at each visit. All measurements will be made by trained coordinators using standard and calibrated instruments.

MGH and UCSD Study subjects

Clinical history and medication reviews OTHER

The following questionnaires will be administered at Screening: Medical history questionnaire Medication use questionnaire Alcohol consumption questionnaire Physical activity questionnaire The following questionnaires will be administered at Visit 1 and Visit 2: Interim medical history questionnaire Change in medication use questionnaire Change in alcohol consumption will be recorded using a modified version of the alcohol use followback. Alcohol use for the 7 day period prior to Visit 1 and for all days between Visit 1 and Visit 2 will be recorded. Change in physical activity questionnaire

MGH and UCSD Study subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (age ≥ 18 years)
• Known or suspected NAFLD based on prior biopsy ≤ 36 months consistent with NAFLD OR
• Abnormal ALT (\>30 U/L for men, \> 19 U/L for women) without other common causes such as HCV, HBV, AND meets criteria within 36 months for ATP III criteria (2005 revision) for metabolic syndrome with any 3 of the 5:
• Waist circumference (WC) \> 102 cm (M) or \> 88 cm (F)
• Fasting glucose ≥ 100 mg/dL or Rx
• TG≥150mg/dLorRx
• SBP \> 130 mmHg
• DBP\>85mmHg or Rx
• Able and willing to participate, including maintaining steady-state: 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 participants, minimum 8, maximum 18), Intermediate likelihood of advanced fibrosis: 1.3 \< FIB-4 \< 2.67 (about one-third of enrolled participants, minimum 8, maximum 18), High likelihood of advanced fibrosis: FIB-4 ≥ 2.67: (about one-third of enrolled participants, minimum 8, maximum 18)

You may not qualify if:

• Liver disease other than NAFLD
• Excess alcohol consumption (≥ 2 units/day for women and ≥ 3 units/day for men)
• Current diagnosis of drug induced liver injury
• Receiving drug or placebo in treatment trial now or within 30 days
• Weight loss or gain of ≥ 5 kg in prior 3 months
• Other factors that in the judgment of the principal investigator might preclude study completion
• 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 ultrasound and VCTE measurements. Women who state they might be pregnant will be required to do a urine pregnancy test to establish eligibility.
• Patients with active implants such as pacemakers or defibrillators or any other contraindication to ultrasound or VCTE scanning.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• University of California, San Diego: collaborator
• Foundation for the National Institutes of Health: collaborator

Study Sites (2)

UC San Diego

San Diego, California, 92103, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Pierce TT, Ozturk A, Sherlock SP, Moura Cunha G, Wang X, Li Q, Hunt D, Middleton MS, Martin M, Corey KE, Edenbaum H, Shankar SS, Heymann H, Kamphaus TN, Calle RA, Covarrubias Y, Loomba R, Obuchowski NA, Sanyal AJ, Sirlin CB, Fowler KJ, Samir AE. Reproducibility and Repeatability of US Shear-Wave and Transient Elastography in Nonalcoholic Fatty Liver Disease. Radiology. 2024 Sep;312(3):e233094. doi: 10.1148/radiol.233094.

  PMID: 39254458 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Blood Specimen Collection; Medication Review

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Medication Systems; Organization and Administration; Health Services Administration; Patient Care Management

Results Point of Contact

• Title: Anthony Samir
• Organization: Massachusetts General Hospital

asamir@mgh.harvard.edu

6178523241

Study Officials

• Anthony E Samir, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Kathryn Fowler, MD

  UC San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Study participants will not be randomized to individual treatment groups. To ensure a uniform distribution of scanner combinations, participants will follow a block-allocation pattern with different scanner combinations for different participants, however, patients and operators will not be blinded to ultrasound scanners being used. All efforts will be made to keep ultrasound operators blinded to clinical and laboratory data, however, it is not believed that this will significantly affect the ultrasound acquisition. The Visit 2 operator will be asked to not review the Visit 1 exam results. Central analysts will be blinded to key clinical and laboratory findings to minimize potential bias. Blinding of the central analysts will be outlined in a separate Image Review Charter.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiologist, Service Chief, Body Ultrasound Imaging Services

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 2, 2021
• Study Start: March 18, 2021
• Primary Completion: November 20, 2021
• Study Completion: November 20, 2021
• Last Updated: July 11, 2023
• Results First Posted: July 11, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (2)