None listed
Conditions
Brief summary
In Australia, nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease, and results in significant healthcare burden from both liver and metabolic complications. NAFLD is defined by the presence of fat in the liver which can cause liver related morbidity and mortality through its progression to liver fibrosis, cirrhosis and increases the risk of developing liver cancer. It is strongly associated with obesity, insulin resistance and the metabolic syndrome, and weight loss is the mainstay of treatment. Weight loss can reduce the amount of fat in the liver, improve the level of liver fibrosis and improve individuals overall metabolic and cardiovascular risk. Current treatment guidelines advise dietary energy restriction, with many recommending a Mediterranean Diet (MD) which has been shown to improve liver fat and reduce the risk of developing T2DM. Despite this current treatment practices are heterogenous, and weight loss is difficult to achieve and maintain. We aim to examine whether the treatment strategies used in the medical management of obesity, such as the use of very low energy diets (VLED) and appetite suppressing (AS) medications, can be adapted to the management of NAFLD which is a related but separate disease entity. This study is a single centre, randomised control trial evaluating the effect of the VLED compared with the standard of care MD in overweight and obese individuals with NAFLD. Participants will be randomised to a 12-week program of either: 1. VLED: a ketogenic 800kcal/day diet utilising meal replacement supplements 2. The standard of care MD: a predominantly plant based diet supplemented with monounsaturated fatty acids (MUFAs) At the end of the 12 week diet, all participants will enter a weight maintenance phase where they will be instructed to follow a calorie controlled but ad-libitum diet in order to maintain their weight, with the VLED group also commenced on low dose Semaglutide as an adjunctive AS medication for 12 weeks. We will compare the impact of these two programs on the severity of NAFLD (change in degree of liver fat on MRI and liver fibrosis on liver biopsy). Other outcome measures include the degree of weight loss and weight maintenance achieved, body composition, and impact on physical activity, mood and quality of life.
Interventions
The intervention is a 12 week 800kcal ketogenic very low energy diet which utilises two optifast meal replacement products per day and one very low carbohydrate meal. The carbohydrate composition of the diet is defined at <=60g of carbohydrates per day. Participants are provided with a recipe book and examples of meals include: mexican beef mince, shredded poached chicken, zucchini enchiladas. Participants undergo face to face education (15-20 minutes duration) about the diet with the trial di
The intervention is a 12 week 800kcal ketogenic very low energy diet which utilises two optifast meal replacement products per day and one very low carbohydrate meal. The carbohydrate composition of the diet is defined at <=60g of carbohydrates per day. Participants are provided with a recipe book and examples of meals include: mexican beef mince, shredded poached chicken, zucchini enchiladas. Participants undergo face to face education (15-20 minutes duration) about the diet with the trial dietician prior to commencement. Optifast meal replacement products are provided to the participants alongside recipe suggestions for their daily meal. Prior to randomisation all participants will undergo a baseline assessment of their fatty liver disease including an MRI performed by a radiographer (approximately 30 minute duration) and interpreted by a radiologist to quantify their liver fat fraction, and an ultrasound guided liver biopsy under local anaesthetic performed by a radiologist (approximately 30 minutes duration) to assess for underlying steatohepatitis and liver fibrosis. Phone support is offered from the dietician at 2, 4 and 9 weeks with a face to face review at 6 weeks. Compliance to the diets will be monitored using a food diary app (easy diet diary) and the intervention group will have ketone levels checked (3-hydroxybutyrate) to assess whether ketosis was achieved. At the end of the diet participants will enter a 12 week weight maintenance phase and be instructed by a dietician to follow an ad libitum calorie controlled diet in order to maintain any weight loss achieved by the dietary intervention. Each participant’s maximum calorie intake is calculated individually (using Schofield equation which incorporates weight, gender, age and reported physical activity levels) and full energy requirements (for weight maintenance) are used to determine dietary prescription. Participants in the intervention arm are no longer provided with meal replacements. Serving sizes are reinforced and support to resume intake within real world setting is provided. To facilitate and record adherence a food diary app is used. The intervention group will also be commenced on low dose semaglutide (0.5mg via subcutaneous injection once weekly for 12 weeks) to assist with weight maintenance during this phase. This will be self administered by participants after education from the trial team. End of intervention assessments including a repeat MRI and liver biopsy will occur at week 24. A final follow up will occur at week 48 to assess for any enduring effects of the intervention.
Sponsors
St Vincent's Hospital Melboourne
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Individuals aged 18 – 70 who are able to provide consent 2. BMI 27kg/m2 to 35kg/m2 3. Elevated ALT and/or GGT 4. >= F1 fibrosis on liver biopsy 5. Liver fat on MRS >= 10%
Exclusion criteria
1. Alcohol >2 SD/day for men and >1 SD/day for women 2. Other liver disease, i.e. viral hepatitis, autoimmune liver disease, haemochromatosis 3. Decompensated cirrhosis or cirrhosis with Fibroscan > 25kPa 4. Other significant medical or psychological issue that would preclude a diet; such as cardiac disease, lung disease or malignancy 5. Antibiotics, probiotics, corticosteroids, hormonal therapies or methotrexate within three months of baseline data collection, or current use of a GLP-1 agonist or insulin 6. Already lost >5% body weight or previous bariatric surgery 7. Participation in another interventional trial, or participation in another interventional trial within the last 6 months
Outcome results
None listed