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| Name | Class |
|---|---|
| University of California, San Diego | OTHER |
| Foundation for the National Institutes of Health | OTHER |
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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.
Study 1.1, is a prospective, 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of Pooled Same-day, Same-operator Repeatability of Shear Wave Speed (SWS) | The same research subject undergoes multiple SWE measurements (in m/s) on multiple devices and transient elastography (TE) at two visits (in 7 days) with different operators. For this outcome measure, the same-day same-operator repeatability is estimated on repeated measurements performed on the same device by the same operator at the same visit. For example, the following structure is followed for a subject; Day1 (Device A, Device B, Device C, TE, Repeated Device A, Repeated Device B), Day2 (Device A, Device B, Device C, TE, Repeated Device C, Repeated TE). The median SWS value (in m/s) is computed for each ultrasound device and is displayed by the TE device. The pooled same-day, same-operator repeatability coefficient of ultrasound measurements of SWS, is reported in the outcome measure data table section. |
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Inclusion Criteria:
Waist circumference (WC) > 102 cm (M) or > 88 cm (F)
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:
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| Name | Affiliation | Role |
|---|---|---|
| Anthony E Samir, MD, MPH | Massachusetts General Hospital | Principal Investigator |
| Kathryn Fowler, MD | UC San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego | San Diego | California | 92103 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39254458 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | MGH and UCSD Study Subjects | NAFLD patients with ultrasound elastography and fat quantification measurements |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | Reproducibility coefficient (in %) | (2 visits, baseline + up to 7 days). Outcome measure will be assessed after pooling measurements from all study subjects. | SWS measurements on ultrasound images | SWS measurements on ultrasound images |
|
8 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MGH and UCSD Study Subjects | NAFLD patients with ultrasound elastography and fat quantification measurements |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anthony Samir | Massachusetts General Hospital | 6178523241 | asamir@mgh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 11, 2021 | Jan 20, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D000090143 | Medication Review |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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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.
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|
| 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 |
|
| 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. |
|
| 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 |
|
| (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. | 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. 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 reproducibility coefficient of measurements obtained across different ultrasound devices on the same day by the same operator is computed. For example, the following structure is followed for a study subject; Day1 (Device A, Device B, Device C, Transient elastography, Repeated Device A, Repeated Device B), Day2 (Device A, Device B, Device C, Transient elastography, Repeated Device C, Repeated transient elastography).The pooled different-scanner, same-day reproducibility coefficient of ultrasound measurements of SWS, 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. |
| Evaluation of Same-day, Same-operator Repeatability of Transient Elastography | Same day same operator repeat median TE measures expressed in m/s are compared and the repeatability is estimated. For example, the following structure is followed for a study subject; Day1 (Device A, Device B, Device C, Transient elastography, Repeated Device A, Repeated Device B), Day2 (Device A, Device B, Device C, Transient elastography, Repeated Device C, Repeated transient elastography), which allows estimation of same-day same operator repeatability. | (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Description |
|---|
| OG000 | MGH and UCSD Study Subjects | Ultrasound based shear wave speed (SWS) and transient elastography based SWS measurements were collected from MGH and UCSD study subjects. SWS and transient elastography measurements are obtained in m/s unit. |
|
|
| Primary | 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. | Posted | Number | Reproducibility coefficient (in %) | (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. | SWS measurements on ultrasound images | SWS measurements on ultrasound images |
|
|
|
| Secondary | Evaluation of Pooled Same-day, Same-operator Repeatability of Shear Wave Speed (SWS) | The same research subject undergoes multiple SWE measurements (in m/s) on multiple devices and transient elastography (TE) at two visits (in 7 days) with different operators. For this outcome measure, the same-day same-operator repeatability is estimated on repeated measurements performed on the same device by the same operator at the same visit. For example, the following structure is followed for a subject; Day1 (Device A, Device B, Device C, TE, Repeated Device A, Repeated Device B), Day2 (Device A, Device B, Device C, TE, Repeated Device C, Repeated TE). The median SWS value (in m/s) is computed for each ultrasound device and is displayed by the TE device. The pooled same-day, same-operator repeatability coefficient of ultrasound measurements of SWS, is reported in the outcome measure data table section. | Posted | Number | Repeatability coefficient (in %) | (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling measurements from all study subjects. | SWS measurements on ultrasound images | SWS measurements on ultrasound images |
|
|
|
| Secondary | Evaluation of Pooled Different-scanner, Same-day Reproducibility of Shear Wave Elastography. | 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. 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 reproducibility coefficient of measurements obtained across different ultrasound devices on the same day by the same operator is computed. For example, the following structure is followed for a study subject; Day1 (Device A, Device B, Device C, Transient elastography, Repeated Device A, Repeated Device B), Day2 (Device A, Device B, Device C, Transient elastography, Repeated Device C, Repeated transient elastography).The pooled different-scanner, same-day reproducibility coefficient of ultrasound measurements of SWS, is reported in the outcome measure data table section. | Posted | Number | Reproducibility coefficient (in %) | (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. | SWS measurements on ultrasound images | SWS measurements on ultrasound images |
|
|
|
| Secondary | Evaluation of Same-day, Same-operator Repeatability of Transient Elastography | Same day same operator repeat median TE measures expressed in m/s are compared and the repeatability is estimated. For example, the following structure is followed for a study subject; Day1 (Device A, Device B, Device C, Transient elastography, Repeated Device A, Repeated Device B), Day2 (Device A, Device B, Device C, Transient elastography, Repeated Device C, Repeated transient elastography), which allows estimation of same-day same operator repeatability. | Posted | Number | Repeatability coefficient (in %) | (2 visits, baseline + up to 7days). Outcome measure will be assessed after pooling all measurements from all study subjects. | SWS measurements on ultrasound images | SWS measurements on ultrasound images |
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|
|
| 0 |
| 40 |
| 0 |
| 40 |
| 0 |
| 40 |
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| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D008509 | Medication Systems |
| D009934 | Organization and Administration |
| D006298 | Health Services Administration |
| D010346 | Patient Care Management |