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Noninvasive Biomarkers of Metabolic Liver Disease 1.1

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ClinicalTrials.gov Identifier: NCT04828551
Recruitment Status : Recruiting
First Posted : April 2, 2021
Last Update Posted : April 2, 2021
Sponsor:
Collaborators:
University of California, San Diego
Foundation for the National Institutes of Health
Information provided by (Responsible Party):
Anthony Samir, Massachusetts General Hospital

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis Nonalcoholic Fatty Liver Device: Ultrasound based shear wave speed and fat quantification methods Diagnostic Test: Blood collection Other: Physical measurements Other: Clinical history and medication reviews Not Applicable

Detailed Description:
This study, Study 1.1, is a prospective, observational, two-center, short- term cross-sectional study to assess the reproducibility and repeatability of a set of specified ultrasound-based quantitative imaging biomarkers. The primary focus will be on imaging biomarkers of the liver fibrosis component of nonalcoholic fatty liver disease (NAFLD), rather than the steatosis or inflammation component. The rationale is that the fibrosis component is linked most closely to survival and other clinical outcomes. Study 1.1 will also collect data to explore vendor- or device-specific investigational biomarkers on other components of NAFLD such as steatosis and possibly inflammation. The data collected will be used to inform a decision of which of these biomarkers have sufficient precision to be advanced to NIMBLE Stage 2.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:

Study participants will not be randomized to individual treatment groups or be blinded. In order to ensure a uniform distribution of scanner combinations, participants will follow a block-randomization 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.

Primary Purpose: Diagnostic
Official Title: Noninvasive Biomarkers of Metabolic Liver Disease 1.1
Actual Study Start Date : March 18, 2021
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : October 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases

Arm Intervention/treatment
MGH and UCSD Study subjects

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
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

Diagnostic Test: Blood collection

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


Other: Physical measurements
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.

Other: Clinical history and medication reviews

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





Primary Outcome Measures :
  1. Pooled different-day, different-operator change of shear wave speed and transient elastography measurements in 2 separate visits [ Time Frame: (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. ]
    As the measurement tool, the results of ultrasound measurements will be pooled and analyzed.


Secondary Outcome Measures :
  1. Evaluation of pooled same-day, same-operator repeatability of shear wave speed [ Time Frame: (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. ]
    As the measurement tool, the results of ultrasound measurements will be pooled and analyzed.

  2. Evaluation of pooled different-scanner, same-day reproducibility of shear wave elastography. [ Time Frame: (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. ]
    As the measurement tool, the results of ultrasound measurements will be pooled and analyzed.

  3. Evaluation of same-day, same-operator repeatability of transient elastography [ Time Frame: (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. ]
    As the measurement tool, the results of transient elastography measurements will be pooled and analyzed.

  4. Evaluation of different-day, different-operator reproducibility of transient elastography [ Time Frame: (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. ]
    As the measurement tool, the results of transient elastography measurements will be pooled and analyzed.

  5. Precision and other reliability metrics of vendor- or device-specific investigational measurements of other components of NAFLD such as steatosis and possibly inflammation. [ Time Frame: (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. ]
    As the measurement tool, the results of transient elastography and ultrasound measurements will be pooled and analyzed.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04828551


Contacts
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Contact: Anthony E Samir, MD, MPH 617-643-2009 asamir@mgh.harvard.edu

Locations
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United States, California
UC San Diego Recruiting
San Diego, California, United States, 92103
Contact: Kathryn Fowler, MD       k1fowler@health.ucsd.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Anthony E Samir, MD, MPH       asamir@mgh.harvard.edu   
Sponsors and Collaborators
Massachusetts General Hospital
University of California, San Diego
Foundation for the National Institutes of Health
Investigators
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Principal Investigator: Anthony E Samir, MD, MPH Massachusetts General Hospital
Principal Investigator: Kathryn Fowler, MD UC San Diego
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Responsible Party: Anthony Samir, Radiologist, Service Chief, Body Ultrasound Imaging Services, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04828551    
Other Study ID Numbers: 2019P002092
First Posted: April 2, 2021    Key Record Dates
Last Update Posted: April 2, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases