Digital Diet and Exercise Intervention to Reduce Liver Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) (DEFIB-MASLD)

Digital Diet and Exercise Intervention to Reduce Liver Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Pilot Randomised Controlled Trial

Study Title: Digital Diet and Exercise Intervention to Reduce Liver Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Randomized Controlled Trial (D-FIB-MASLD)

Objective:

This study aims to assess whether a digital application called Gro Health can help patients with MASLD and significant liver fibrosis reduce their liver stiffness. Liver stiffness is a measure of liver health and fibrosis. The study will also investigate the impact of this intervention on weight, body measurements, liver health markers, and overall quality of life.

Background:

MASLD is a liver condition linked to metabolic issues such as obesity and diabetes. It is a common cause of liver-related complications and can lead to severe liver damage. Lifestyle changes, like improved diet and exercise, are key to managing MASLD, but achieving these changes can be challenging for many patients. Digital tools like the Gro Health app may provide personalized and accessible support to improve outcomes.

Study Design:

This is a randomized controlled trial involving 100 participants with MASLD and significant fibrosis. Participants will be assigned to either the intervention group (using the Gro Health app) or a control group (receiving standard care). The study will take place at a single site over 12 months.

Intervention:

Participants in the intervention group will use the Gro Health app, which offers personalized calorie and activity goals, a food diary, over 1,000 Mediterranean diet recipes, and educational resources. They will also receive a smartwatch to track steps and physical activity. The app includes a feature allowing researchers to monitor participants' engagement and provide encouragement.

Eligibility:

Adults aged 18 or older with a diagnosis of MASLD and a liver stiffness measurement of 8 kPa or higher are eligible. Key exclusions include alcohol consumption over 14 units/week, a BMI over 40, or certain other liver diseases or medications.

Outcomes:

The primary outcome is a reduction in liver stiffness after six months. Secondary outcomes include changes in weight, BMI, body fat percentage, liver enzymes, cholesterol, and quality of life. Additional data on app usage, physical activity, and dietary habits will also be collected for the intervention group.

Potential Impact:

If successful, this study will provide evidence that digital tools can help improve liver health and overall well-being in patients with MASLD, offering a scalable solution for healthcare systems.

Study Overview

• Status: Not yet recruiting
• Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease
• Intervention / Treatment: Device: Gro Health digital application

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Caroline Gosson, MBBS; Phone Number: +4475902577755; Email: caroline.gosson@stgeorges.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SW170QT
    • St George's University Hospitals NHS Foundation Trust
    • Contact: Caroline Gosson, MBBS; Phone Number: +447590257755; Email: caroline.gosson@stgeorges.nhs.uk
    • Contact: Email: caroline.gosson@stgeorges.nhs.uk
    • Contact: Caroline Gosson, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults 18 years and over
• Diagnosis of MASLD made by a hepatologist
• Vibration-Controlled Transient Elastography (VCTE) (FibroScan) liver stiffness measurement (LSM) 8 kPa and above
• Able to provide written consent
• Own a smartphone with data plan

Exclusion Criteria:

• Alcohol consumption >14 units/week
• BMI >40
• Liver disease due to: Alcohol including MASLD with increased alcohol intake (MetALD), Any viral hepatitis, Autoimmune and cholestatic aetiologies including, but not limited to, primary biliary cholangitis and primary sclerosing cholangitis, Hereditary aetiologies including, but not limited to, haemachromatosis, Wilson's disease, alpha-1-antitrypsin deficiency
• Currently under investigation for cancer or receiving treatment for active cancer
• Myocardial infarction within last 6 months or uncontrolled cardiovascular disease
• Pregnant or planning
• Currently or due to be taking any of the following drugs: GLP-1/GIP agonists, Systemic high dose corticosteroids for >6 weeks, Tamoxifen, Amiodarone, Methotrexate, Lomitapide, Valproate, Irinotecan, 5-Fluoruracil
• Currently using or enrolled in any other lifestyle intervention application or weight loss programme
• Undergone or due to undergo bariatric surgery including bariatric endoscopic procedures
• Any other intercurrent illness that is either life-threatening or of clinical significance such that it might limit compliance with study procedures, in the Investigator's opinion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gro Health Application; The Gro Health digital application is a personalised treatment platform proven to support sustainable weight loss. It is non-MHRA regulated as MASLD is within the device's UKCA/CE UKNI/CE marked indication. Gro Health reports 7% weight loss at 52 weeks in patients with Type 2 Diabetes Mellitus. We can set up the application so patients follow a Mediterranean diet. Over 1000 recipes of different cuisines will be available, along with weekly diet plans and shopping lists. Based on the patient's body mass index, daily calories and macronutrient targets will be calculated in line with the Mediterranean diet. Aerobic exercise can be tracked by daily step count linked by compatible smartwatches and smartphones. Physical activity can also be logged manually. Gro Health provides educational videos on aerobic and resistance exercise, along with 'follow along' videos of exercises for patients. These videos range from ones for beginners to those who have more experience with exercise.	Device: Gro Health digital application; The Gro Health digital application is a personalised treatment platform proven to support sustainable weight loss. It is non-MHRA regulated as MASLD is within the device's UKCA/CE UKNI/CE marked indication. Gro Health reports 7% weight loss at 52 weeks in patients with Type 2 Diabetes Mellitus. We can set up the application so patients follow a Mediterranean diet. Over 1000 recipes of different cuisines will be available, along with weekly diet plans and shopping lists. Based on the patient's body mass index, daily calories and macronutrient targets will be calculated in line with the Mediterranean diet. Aerobic exercise can be tracked by daily step count linked by compatible smartwatches and smartphones. Physical activity can also be logged manually. Gro Health provides educational videos on aerobic and resistance exercise, along with 'follow along' videos of exercises for patients. These videos range from ones for beginners to those who have more experience with exercise.
No Intervention: Standard of Care; If randomised to this arm, participants will not receiving any additional intervention beyond their usual clinical care for their condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome measure is change in liver stiffness measurement at 6 months compared to baseline	The primary outcome measure is change in liver stiffness measurement (LSM) at 6 months compared to baseline. LSM is measured in kPa. Vibration controlled transient elastography (VCTE) has been validated as a measure of fibrosis across a wide spectrum of chronic liver diseases including MASLD. Whilst liver histology remains the gold standard for fibrosis staging, and magnetic resonance imaging and elastography for non-invasive hepatic lipid quantification and fibrosis respectively, both techniques are largely limited by being time consuming and expensive. VCTE provides multiple advantages of low cost, short procedure time, immediate result availability, good reproducibility and the ability to be performed in an outpatient setting. Studies have shown that LSM has good accuracy for liver-related events and mortality. Change in LSM has been shown to correlate with the risk of liver-related events and death.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight in kilograms - To compare the effect of a digital application based lifestyle intervention to standard of care on weight	Baseline weight in kilograms will be taken at day 0 on calibrated hospital scales in clinic from all study participants. A formal weight will be taken at all hospital clinic appointments and at 26 weeks and at the end of the intervention period. Only weights taken on the calibrated hospital scales will be used for analysis.	6 and 12 months
Percentage weight loss - To compare the effect of a digital application based lifestyle intervention to standard of care on percentage weight loss	Baseline weight in kilograms will be taken at day 0 on calibrated hospital scales in clinic from all study participants. A formal weight will be taken at all hospital clinic appointments and at 26 weeks and at the end of the intervention period. Only weights taken on the calibrated hospital scales will be used for analysis.	6 and 12 months
Height in metres	Height in metres will be taken at baseline for the use in BMI calculation as stated for BMI outcome	baseline
Body mass index - To compare the effect of a digital application based lifestyle intervention to standard of care on BMI	Baseline weight in kilograms will be taken at day 0 on calibrated hospital scales in clinic from all study participants. Baseline height will be taken at day 0 only. A formal weight will be taken at all hospital clinic appointments and at 26 weeks and at the end of the intervention period. Only weights taken on the calibrated hospital scales will be used for analysis.	6 and 12 months
Body fat percentage - To compare the effect of a digital application based lifestyle intervention to standard of care on body fat percentage	Measured at baseline, 26 weeks and at the end of the intervention period using Withings smart scale	6 and 12 months
Controlled Attenuation Parameter - To compare the effect of a digital application based lifestyle intervention to standard of care on CAP.	CAP is a measure of liver fat taken by Vibration Controlled Transient Elastography (also known as Fibroscan). Baseline CAP will be taken on day 0 using FibroScan machine by a trained operator who is not involved in the trial from all study participants. A reading will be taken at 26 weeks and at the end of the intervention period.	6 and 12 months
Spleen stiffness measurement - To compare the effect of a digital application based lifestyle intervention to standard of care on SSM	Spleen stiffness measurement is measured by vibration controlled transient elastography (also known as Fibroscan) and indicates spleen scarring. Baseline SSM will be taken on day 0 using FibroScan machine by a trained operator who is not involved in the trial from all study participants. A reading will be taken at 26 weeks and at the end of the intervention period.	6 and 12 months
To compare the effect of a digital application based lifestyle intervention to standard of care on the following blood parameters: alanine transaminase ALT, aspartate aminotransferase AST, HbA1c	Concentration of ALT, AST, HbA1c in blood samples will be taken on day 0, 26 weeks and at the end of the intervention period from all participants if not taken within the last 3 months	6 and 12 months
To compare the effect of a digital application based lifestyle intervention to standard of care on the following blood parameters: total cholesterol, low-density lipoprotein cholesterol LDL, high-density lipoprotein cholesterol HDL, triglycerides	Concentration of total cholesterol, LDL, HDL and triglycerides in blood samples will be taken on day 0, 26 weeks and at the end of the intervention period from all participants if not taken within the last 3 months.	6 and 12 months
Waist and hip circumference - To compare the effect of a digital application based lifestyle intervention to standard of care on these measurements	Baseline waist and hip circumference will be measured on day 0 using a tape measure in centimetres at the midpoint between the lower margin of the last palpable rib and the top of the iliac crest as recommended by the WHO from all study participants. A measurement will be taken at 26 weeks and at the end of the intervention period.	6 and 12 months
Systolic blood pressure - To compare the effect of a digital application based lifestyle intervention to standard of care on blood pressure	Baseline systolic blood pressure will be taken on day 0 from all study participants. A reading will be taken at 26 weeks and the end of the intervention period using a calibrated electronic sphygmomanometer.	6 and 12 months
16. Echosens Agile 3+ score - composite score comprising LSM, ALT, AST, platelets, age, gender, diabetic status	Agile 3+ score will be calculated from baseline LSM, ALT, AST, platelets, age, gender and diabetic status and again calculated using the same parameters taken at 26 weeks and at the end of the intervention period.	6 and 12 months
Health-related Quality of Life assessment - EuroQol EQ-5D-5L to compare the effect of a digital application based lifestyle intervention to standard of care on these	Health-related Quality of Life will be measured using the EuroQol EQ-5D-5L on day 0, 26 weeks and at the end of the intervention by all participants.	6 and 12 months
Health-related Quality of Life assessment - Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis (CLDQ-NASH)) - To compare the effect of a digital application based lifestyle intervention to standard of care on these	Health-related Quality of Life will be measured using the Chronic Liver Disease Questionnaire for Non-alcoholic Steatohepatitis (CLDQ-NASH) on day 0, 26 weeks and at the end of the intervention by all participants.	6 and 12 months
Hospital Anxiety and Depression Scale (HADS) - To compare the effect of a digital application based lifestyle intervention to standard of care on HADS	Hospital Anxiety and Depression Scale will be measured on day 0, 26 weeks and at the end of the intervention period by all participants	6 and 12 months
Number of patients with improvement in liver stiffness measurement LSM - To compare the effect of a digital application based lifestyle intervention to standard of care on number of patients with improvement in LSM	The total number of patients with improvement in LSM in each group	6 and 12 months
Liver stiffness measurement - same at primary outcome measure, but at 12 rather than 6 months	The primary outcome measure is change in liver stiffness measurement (LSM) at 6 months compared to baseline. This secondary outcome is that same measure but at 12 months to see if results are sustained. LSM is measured in kPa. VCTE has been validated as a measure of fibrosis across a wide spectrum of chronic liver diseases including MASLD. Whilst liver histology remains the gold standard for fibrosis staging, and magnetic resonance imaging and elastography for non-invasive hepatic lipid quantification and fibrosis respectively, both techniques are largely limited by being time consuming and expensive. VCTE provides multiple advantages of low cost, short procedure time, immediate result availability, good reproducibility and the ability to be performed in an outpatient setting. Studies have shown that LSM has good accuracy for liver-related events and mortality. Change in LSM has been shown to correlate with the risk of liver-related events and death.	12 months
Assess the frequency of digital lifestyle application interaction	Gro Health can provide data of individual patient's application usage in the form of total number of 'application openings'. In the intervention group, we would assess whether the participants with more app openings have a greater improvement in their VCTE LSM.	12 months
Assess the change in daily step count	In the intervention group, daily step count electronically recorded by compatible smartwatch. Measure mean weekly step count and how this changes over the 12 month period.	12 months
Assess the change in amount and type of physical activity	In the intervention group, in addition to daily step count, physical activity can be manually logged by patient (time and date of activity, type of activity and activity duration). Measure weekly total minutes of physical activity and how this changes over the 12 month period.	12 months
Assess the change in self-recorded weights	In the intervention group, we would assess the trend in weight loss over the 12 month period	12 months
Assess the frequency of food diary usage	In the intervention group, we would assess how frequently participants log food and how this changes over time	12 months
Assess the interaction with educational content	Percentage of total educational content reviewed by 12 months. Assess if there is a correlation between amount of educational content reviewed and if this leads to a greater reduction in VCTE LSM.	12 months
Number of personalised messages sent to participant over 12 month period	In the intervention group, personalised messages will be sent at least monthly and also ad hoc. We would assess whether the number of messages correlates with change in VCTE LSM.	12 months
Total minutes of telephone calls to participant over 12 month period	In the intervention group, telephone calls will be made to participants at 1 week and then ad hoc. We would assess whether the number of minutes correlates with change in VCTE LSM.	12 months

Collaborators and Investigators

• Sponsor: St. George's Hospital, London

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 29, 2025
• First Submitted That Met QC Criteria: April 2, 2025
• First Posted (Actual): April 9, 2025

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Fatty liver; Digital health; Non-alcoholic Fatty Liver Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Fibrosis; Liver Diseases; Liver Cirrhosis
• Other Study ID Numbers: StGeorgesLondon

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No