Signature Diagnostic of Non-alcoholic Steatohepatitis (NASH) by Infrared Light Spectroscopy

Obesity Clinical Trial

— SIGNALS  

Official title:

Validation Study of the NASHMIR Test for Non-alcoholic Steatohepatitis (NASH) Diagnosis in Patients With Severe or Morbid Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03978247
• Other study ID #: SIGNALS - 01
• Secondary ID: 2018-A03240-55
• Status: Completed
• Phase: N/A
• Start date: June 21, 2019
• Est. completion date: October 31, 2020

Study information

• Verified date: February 2021
• Source: Diafir
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluation of the diagnostic performance of an algorithm developed to detect metabolic profiles specific of non-alcoholic steatohepatitis NASH and based on the reading of a blood sample's infrared spectra

Description:

The study is aimed at patients suffering from severe or morbid obesity and engaged in a bariatric surgery course. An additional blood sample will be taken upstream of the surgical procedure in the fasted subject. The metabolic fingerprint of the patient will be analyzed on serum from spectral data measured at most two hours after collection. The spectra obtained by the spectroscopy platform will be processed by algorithmic analysis to build the diagnostic test. During the surgical procedure, a liver biopsy will be performed. The sample will be sent to the pathology laboratory for preparation and the slides will then be anonymized to be sent to a specialized laboratory for centralized reading by an expert pathologist. This expert will determine the diagnosis of non-alcoholic steatohepatitis (NASH) or non-NASH after microscopic analysis of the sample without having any information about the patient. The two results obtained by the spectroscopic test and by means of the biopsy will then be compared to determine the diagnostic performance of the developped test (NASHMIR test).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 382
• Est. completion date: October 31, 2020
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patient over 18 years old;
• Patient able to read, write and understand the French language;
• Patient who has signed an informed consent form before carrying out any procedure related to the study;
• Patient supported in bariatric surgery;
• Patient affiliated to a social security scheme or comparable scheme

Exclusion Criteria:

• Patient who has already benefited from a bariatric surgery (ring, sleeve, bypass ..);
• Patient taking: corticosteroid for more than 2 months, amiodarone, methotrexate, tamoxifen, 5-fluorouracil, irinotecan, cisplatin, asparaginase, nucleoside reverse transcriptase inhibitors of HIV, tetracycline, valproic acid, perhexilline;
• Patient with excessive alcohol consumption (> 210 g/week in men,> 140 g/week in women) present or past;
• Patient with infection or coinfection present or passed with hepatitis B virus, hepatitis C virus or human immunodeficiency virus;
• Patient with known chronic liver disease (including hemochromatosis, autoimmune hepatitis ...);
• pregnant, parturient or nursing women;
• Patient deprived of liberty by judicial or administrative decision;
• Patient subject to a legal protection measure;

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Obesity

Intervention

Diagnostic Test:
• NASHMIR
An additional blood sample will be taken upstream of the surgical procedure and a liver biopsy will be performed in all included patients. The two results obtained by the spectroscopic test and by means of the biopsy will then be compared to determine the diagnostic performance of the developped test (NASHMIR test).

Locations

Country	Name	City	State
Belgium	CHU de Liège	Liège

Sponsors (2)

Lead Sponsor	Collaborator
Diafir	Clinact

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic performance	The comparison of the results obtained by the mathematical analysis of the infrared spectra with those obtained by the reference method on histological samples from liver biopsies will allow to classify the results in true-positive, false-positive, true-negative and false-negative.; The diagnostic performance of the signature will be evaluated by calculating the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio values.	0-12 months
Secondary	Diagnostic performance considering size	Diagnostic performance of the test taking into account size (cm). Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering current weight	Diagnostic performance of the test taking into account current weight (kg). Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering weight of the patient at the age of 20	Diagnostic performance of the test taking into account Weight of the patient at the age of 20 (kg).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering body mass index	Diagnostic performance of the test taking into account BMI (Body Mass Index) (kg/m2).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering waist	Diagnostic performance of the test taking into account waist (cm). Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering hip circumference	Diagnostic performance of the test taking into account Hip circumference (cm). Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering systolic blood pressure	Diagnostic performance of the test taking into account systolic blood pressure (mmHg).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering diastolic blood pressure	Diagnostic performance of the test taking into account diastolic blood pressure (mmHg).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering type 2 diabetes	Diagnostic performance of the test taking into account type 2 diabetes (yes/No).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering sleep apnea	Diagnostic performance of the test taking into account sleep apnea (Yes/No). Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering alcohol consumption	Diagnostic performance of the test taking into account current and/or previous alcohol consumption (Date and number of drinks per week).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering tobacco consumption	Diagnostic performance of the test taking into account current and/or previous tobacco consumption (date and number of pack of cigarettes per year).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering coffee consumption	Diagnostic performance of the test taking into account coffee consumption (number of cups per day).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering cannabis consumption	Diagnostic performance of the test taking into account cannabis consumption (number of joints per week).; Significance of each clinical parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant clinical variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the hemoglobin concentration	Diagnostic performance of the test taking into account the hemoglobin concentration (g/100mL).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the mean corpuscular volume	Diagnostic performance of the test taking into account mean corpuscular volume (fL).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the leukocyte count	Diagnostic performance of the test taking into account leukocyte count (Giga/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the platelet count	Diagnostic performance of the test taking into account platelet count (Giga/L). Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of aspartate transaminase	Diagnostic performance of the test taking into account aspartate transaminase (UI/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of alanine aminotransferase	Diagnostic performance of the test taking into account alanine aminotransferase (UI/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of gamma-glutamyl transferase	Diagnostic performance of the test taking into account the concentration of gamma-glutamyl transferase (UI/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of bilirubin	Diagnostic performance of the test taking into account the concentration of bilirubin (mg/dL).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of alkaline phosphatase	Diagnostic performance of the test taking into account the concentration of alkaline phosphatase (UI/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the prothrombin time	Diagnostic performance of the test taking into account the prothrombin time (%).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the blood glucose level	Diagnostic performance of the test taking into account the blood glucose level (mmol/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the HbA1c level	Diagnostic performance of the test taking into account the HbA1c level (hemoglobin A1c) (%).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of total cholesterol	Diagnostic performance of the test taking into account the concentration of total cholesterol (mmol/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of HDL cholesterol	Diagnostic performance of the test taking into account the concentration of HDL cholesterol (mmol/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of LDL cholesterol	Diagnostic performance of the test taking into account the concentration of LDL cholesterol (mmol/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of triglycerides	Diagnostic performance of the test taking into account the concentration of triglyceride (mmol/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of C reactive protein	Diagnostic performance of the test taking into account the concentration of C reactive protein (mg/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of ferritin	Diagnostic performance of the test taking into account the concentration of ferritin (g/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the concentration of albumin	Diagnostic performance of the test taking into account the concentration of albumin (g/L).; Significance of each biological parameter will be assessed using statistical tests (mean comparison) on the two main populations (Non Alcoholic Steato Hepatitis Yes or No). Using logistic regression, a score calculated with significant biological variables will be aggregated to spectral score (primary outcome) in order to assess new diagnostic performance.	0-12 months
Secondary	Diagnostic performance considering the subtype of non-alcoholic steatohepatitis determined through analysis of biopsy samples	Diagnostic performance of the test according to the different subtypes of non-alcoholic steatohepatitis (NAS score). NAFLD Activity Score calculated according to the steatosis grade (0, 1, 2 or 3), level of lobular inflammation (0, 1, 2 or 3) and stages of liver cell injury (0, 1 or 2)	0-12 months