Viewing Study NCT06203548



Ignite Creation Date: 2024-05-06 @ 7:58 PM
Last Modification Date: 2024-10-26 @ 3:17 PM
Study NCT ID: NCT06203548
Status: RECRUITING
Last Update Posted: 2024-01-12
First Post: 2024-01-02

Brief Title: Monitoring Changes in Hepatic Steatosis Using Continuous Controlled Attenuation Parameter
Sponsor: Chinese University of Hong Kong
Organization: Chinese University of Hong Kong

Study Overview

Official Title: Monitoring Changes in Hepatic Steatosis During a Lifestyle Intervention Programme in Patients With Non-alcoholic Fatty Liver Disease Using the Novel Continuous Controlled Attenuation Parameter Versus MRI Proton Density Fat Fraction
Status: RECRUITING
Status Verified Date: 2024-08
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: Background Non-alcoholic fatty liver disease NAFLD affects 30 of the Asian adult population and is emerging as one of the important leading causes of liver cancer and cirrhosis Although a number of biomarkersmany have been developed for the assessment of liver fat and fibrosis most existing studies were cross-sectional in nature The role of these biomarkers for monitoring and response assessment remains elusive At present magnetic resonance imaging proton density fat fraction MRI-PDFF is considered the gold standard to in quantifying liver fat The MRI-PDFF response defined as a 30 relative reduction in liver fat fraction has been shown to correlate with improved hepatic inflammation and fibrosis However MRI is limited by cost and availability The cContinuous controlled attenuation parameter CAPc measurement by vibration controlled transient elastography is a new technology to quantify liver fat It is a point-of-care test and has the potential to replace the MRI-PDFF as a monitoring and response biomarker in routine practice

Study plan This prospective cohort study will include 150 patients with NAFLD who will join a 6-month lifestyle modification programme involving dietary intervention and physical training This will create a cohort of varying degrees of liver fat reduction Using MRI-PDFF as the reference standard we will evaluate the accuracy of a changes in CAPc in reflecting the MRI-PDFF response and remission of NAFLD with all non-invasive tests performed at screening and Month 6 In addition we will test the hypothesis that the the change in CAPc is superior to the change of in other steatosis tests results including the original CAP abdominal ultrasonography and steatosis scores of fatty liver index hepatic steatosis index NAFLD liver fat score and NAFLD ridge score in predicting the MRI-PDFF response The area under the receiver-operating characteristics curve of the CAPc response in predicting the MRI-PDFF response will be compared with that of the other steatosis tests using the DeLong test
Detailed Description: STUDY DESIGN OVERVIEW In order to evaluate the use of continuous CAP to monitor changes in liver fat over time we need a cohort of patients with varying degree of liver fat reduction Therefore we will enrol MASLD patients in a lifestyle intervention programme With this design we will measure original CAP continuous CAP and MRI-PDFF in all patients at baseline and Month 6 As described in the introduction MRI-PDFF is an accurate and reliable non-invasive test to quantify liver fat and will serve as the reference standard in this study

5 CLINIC VISITS AND ASSESSMENTS Clinic visits The patients will attend 4 clinic visits screening baseline month 3 and month 6

Procedures at the screening visit

Obtain informed written consent
Verify conformance with the study inclusion and exclusion criteria
Record medical history
Record smoking and alcohol consumption with standard questionnaires
Physical examination
Blood tests including complete blood count prothrombin time renal function test and liver biochemistry including alanine aminotransferase ALT aspartate aminotransferase AST and gamma-glutamyl transpeptidase GGT lipids plasma glucose and HbA1c
Hepatitis B surface antigen and anti-hepatitis C virus antibody
Vibration-controlled transient elastography examination
Bedside abdominal ultrasonography The diagnosis of fatty liver will be based on the presence of bright liver echotexture deep attenuation of ultrasound signal and blurring of hepatic vasculature19
Arrange MRI-PDFF examination within 1 week of VCTE examination The short interval is to avoid significant change in liver fat between the non-invasive measurements of liver fat by original CAP continuous CAP and MRI-PDFF

Procedures at the baseline visit

Verify conformance with the study inclusion and exclusion criteria based on additional laboratory and MRI-PDFF results
Document new symptoms and adverse events if any
Record smoking and alcohol consumption with standard questionnaires
Document dietary intake over a 1-week period using a locally validated food frequency questionnaire20
Complete the International Physical Activity Questionnaire
Physical examination including measurement of the patients body height body weight waist circumference hip circumference and blood pressure
Body composition measurement
After overnight fasting for at least 8 hours blood tests including complete blood count prothrombin time renal function test liver biochemistry including ALT AST and GGT plasma glucose HbA1c insulin and neuregulin 4
and lipid profile including high density lipoprotein HDL- and low density lipoprotein LDL-cholesterol
Serum plasma and buffy coat samples will be stored for 15 years for future biochemical and genetic studies optional with separate consent

Month 3 visit

Document new symptoms and adverse events if any
Record smoking and alcohol consumption with standard questionnaires
Document dietary intake over a 1-week period using a locally validated food frequency questionnaire20
Complete the International Physical Activity Questionnaire
Physical examination including measurement of the patients body height body weight waist circumference hip circumference and blood pressure
Body composition measurement
After overnight fasting for at least 8 hours blood tests including complete blood count prothrombin time renal function test liver biochemistry including ALT AST and GGT levels plasma glucose HbA1c insulin neuregulin 4 and lipid profile including HDL- and LDL-cholesterol
Serum and plasma samples will be stored for 15 years for future biochemical studies optional with separate consent
Vibration-controlled transient elastography examination

Month 6 visit end of study

Document new symptoms and adverse events if any
Record smoking and alcohol consumption with standard questionnaires
Document dietary intake over a 1-week period using a locally validated food frequency questionnaire20
Complete the International Physical Activity Questionnaire
Physical examination including measurement of the patients body height body weight waist circumference hip circumference and blood pressure
Body composition measurement
After overnight fasting for at least 8 hours blood tests including complete blood count prothrombin time renal function test liver biochemistry including ALT AST and GGT levels plasma glucose haemoglobin A1c insulin neuregulin 4 and lipid profile including HDL- and LDL-cholesterol
Serum and plasma samples will be stored for 15 years for future biochemical studies optional with separate consent
Bedside abdominal ultrasonography The diagnosis of fatty liver will be based on the presence of bright liver echotexture deep attenuation of ultrasound signal and blurring of hepatic vasculature19
Vibration-controlled transient elastography examination
Arrange MRI-PDFF examination within 1 week

Lifestyle modification programme In order to produce a patient cohort with various degree of liver fat reduction over time the patients will participate in a lifestyle modification programme led by dietitians for 6 months Details of the programme have been described6 All patients will attend sessions weekly in the first 2 months and monthly in the remaining 4 months The programme focuses on reducing caloric intake and increasing energy expenditure At the first visit the dietitian will perform a complete behavioural assessment including the patients eating and lifestyle patterns specific eating-related behaviours knowledge concerns and feelings A target body weight will be set During follow-up visits the dietitian will review the patients dietary pattern and provide recommendations Each patient will be given an individualised meal plan The dietary component and portion size are based on recommendations by the American Dietetic Association with emphasis on fruit and vegetables moderate-carbohydrate low-fat low-glycaemic index and low-calorific products in appropriate portions The patients will be taught techniques to cope with at-risk situations such as parties and festival celebrations In addition the patients will be encouraged to have a combination of aerobic exercise and resistance training with intensity and frequency following the Physical Activity Guidelines21

Vibration controlled transient elastography CAP and liver stiffness will be measured by vibration controlled transient elastography FibroScan Echosens Paris France by operators who have performed at least 500 examinations in the past according to the training and instructions by the manufacturer22 Our centre is equipped with both the FibroScan 502 Touch and FibroScan 630 Expert machines The former is used for original CAP measurements whereas the latter is equipped with the SmartExam software and can be used for continuous CAP measurements We will choose the M or XL probes according to the machines automatic probe selection tool

MRI-PDFF We will perform MRI-PDFF within 1 week from the clinic visit and transient elastography examination We will use a 3T whole-body scanner Achieva TX Philips Healthcare the Netherlands23 We will use the MRI machine that belongs to The Chinese University of Hong Kong Thus the study will not affect the service of the hospital The protocol uses a gradient echo sequence with a low flip angle to minimize T1 bias and it acquires multiple echoes in which fat and water signals are in or out of phase with respect to each other After acquiring the data at each echo an algorithm estimates and corrects T2 effects and calculates the liver fat content by estimating fat and water proton densities The field of view for the sequences to used will cover the whole abdomen from the xiphoid process to the symphysis pubis to include the whole liver pancreas and whole abdominal subcutaneousvisceral adipose tissue Fatty liver is defined as an intrahepatic triglyceride content of 5 or more Two operators will analyse the MRI-PDFF results for liver and pancreatic fat to ensure a high inter-observer agreement Additionally a non-breath-hold acquisition will be performed from the base of the skull to the base of the thoracic cavity for neck and supraclavicular adipose tissue measurements including brown adipose tissue

Steatosis scores Based on the clinical and laboratory parameters obtained at baseline and Month 6 we will calculate steatosis scores to determine the presence and resolution of MASLD Appendix

Abdominal ultrasonography Abdominal ultrasonography will be performed on the same day as clinical assessment by experienced hepatologists or radiographers who are blinded to all clinical and laboratory data The examination will be performed using a 5 MHz transducer and a high-resolution B-mode scanner To ensure consistency across the participating sites we will use the Hamaguchi system to score the liver for 1 bright liver and hepatorenal echo contrast 0-3 points 2 deep attenuation 0-2 points and 3 vessel blurring 0-1 point19 A score of 2 has 92 sensitivity and 100 specificity for the diagnosis of MASLD

For exploratory purpose attenuation imaging ATI during ultrasonography will be performed in around half of the subjects n75 An Aplio i800 Canon medical systems Tochigi Japan ultrasound machine will be used Using a 1 to 8MHz convex transducer i8CX1 the liver parenchyma will be first evaluated on B-mode to ensure that the fan shaped sampling box is placed in a homogenous region thereafter the ATI mode will be activated All images will be obtained in the supine position and in the intercostal planes with the transducer perpendicular to the skin An approximately 4 x 8cm sampling box will be positioned randomly in the liver including the left lobe 2 cm below the capsule during several seconds of breath-holding Non-homogeneous areas such as large vessels and cystic structures are automatically excluded from the ATI map using a system inherent structure removal filter Thus homogenous ATI colour maps will be acquired as much as possible By careful avoidance of large vessels and areas of reverberation artifacts a 2 x 4cm region of interest for measurement will be set within the sampling box of ATI and placed in the middle portion of the sampling box to reduce the intra-observer variability Attenuation Coefficient with R2 092 will be regarded as valid measurement ATI examinations will be performed in five valid Attenuation Coefficient dBcmMHz measurements of which the median value of the measurements will be used for analysis The estimated scan time is 10 minutes

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None