Metabolic Associated-dysfunction Steatotic Liver Disease (MASLD)
Conditions
Keywords
time-restricted feeding, intermittend fasting, 5:2 fasting, steatotic liver disease, MASLD, liver health, dietary intervention, nutrition, lifestyle intervention
Brief summary
The recommended treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) currently focuses on lifestyle changes, including dietary adjustments and increased physical activity. Intermittent fasting is a specific dietary approach in which food intake is restricted for certain periods. Recent scientific evidence suggests that intermittent fasting can positively influence body weight, insulin resistance, and markers of inflammation. This study will examine whether restricting energy intake to approximately 600 kcal on two days per week has beneficial effects on MASLD. The nutritional framework is based on the guidelines of the German Nutrition Society (DGE) for a healthy diet (10 rules for healthy eating). Following a two-week introduction to these DGE recommendations, participants will be randomly assigned to one of two treatment groups. In the intervention group, participants follow a 5:2 intermittent fasting regimen, eating without restrictions on five days per week and limiting intake to about one-quarter of their usual daily energy (≈600 kcal) on two non-consecutive days. In the control group, participants follow a healthy diet according to DGE guidelines without restrictions on timing or energy intake.
Interventions
BEHAVIORALtime-restricted feeding in a 5:2 regimen
Participants in the intervention group follow a 5:2 intermittent fasting regimen, consisting of two non-consecutive days per week with a reduced energy intake of approximately 600 kcal, while on the remaining five days they adhere to a balanced diet in accordance with the recommendations of the German Nutrition Society (DGE).
Sponsors
Universität des Saarlandes
M3 Research Center, Dr. Suchira Gallage
Center for Molecular Signaling, Prof. Dr. Daniela Yildiz
Department of Internal Medicine I, University Medical Centre Mainz, Prof. Dr. Peter R. Galle und PD Dr. Christian Labenz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 18 and 75 years * Body mass index (BMI) \> 25 kg/m² * MASLD grade 3 with CAP ≥ 280 dB/m, excluding liver damage * Liver stiffness \< 13 kPa * Ability to understand the study and the individual consequences of participating in the study * Signed and dated consent form before the start of any study activity
Exclusion criteria
* Hepatocellular carcinoma or non-curatively treated carcinomas * Alcohol consumption \>20 g (women) and \>30 g (men) per day * Other liver diseases (HBV, HCV, HDV, HEV, HIV), autoimmune diseases or chronic cholestatic liver disease, hereditary haemochromatosis, Wilson's disease, α-1-antitrypsin deficiency * Medications that cause liver disease or secondary NAFLD (e.g. tamoxifen, systemic corticosteroids, methotrexate, tetracyclines, oestrogens, valproic acid) * Body weight changes of \> 5% in the last 6 months * Statins and/or other lipid-lowering drugs, if these have not been taken in a stable dose for at least 4 weeks * Uncontrolled type 2 diabetes defined as HbA1c value \> 9.0% or insulin-dependent type 2 diabetes * Pregnancy * Immunological or inflammatory diseases (e.g. systemic lupus erythematosus) * Following a restrictive, special diet * Patients who have undergone organ transplants * Lack of or absence of capacity to give consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of controlled attenuation parameter (CAP) | from enrollment to the end of treatment at 12 weeks | The Controlled Attenuation Parameter (CAP) is a non-invasive ultrasound-based measure obtained during transient elastography (FibroScan®). CAP quantifies the attenuation of ultrasound signals as they pass through the liver, which correlates with the degree of hepatic steatosis. It is expressed in decibels per meter (dB/m). In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), CAP is widely used to assess and grade liver fat content. Higher CAP values reflect greater hepatic fat accumulation. An improvement is defined as a reduction in CAP value of at least 20 dB/m compared to the baseline value |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in liver stiffness measurment (LSM) | from enrollment to the end of treatment at 12 weeks | Liver stiffness measurement (LSM) is a non-invasive technique used to assess hepatic fibrosis. It is most commonly performed using transient elastography (FibroScan®), which measures the velocity of a shear wave generated by a mechanical pulse through the liver tissue. The faster the wave propagates, the stiffer the liver, reflecting the degree of fibrosis. Results are expressed in kilopascals (kPa). In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), LSM provides valuable information on fibrosis stage and risk of progression to advanced liver disease, including cirrhosis. |
| Improvement in CLDQ-NAFLD/NASH for liver-specific quality of life | from enrollment to the end of treatment at 12 weeks | The CLDQ (Chronic Liver Disease Questionnaire) is a validated questionnaire for assessing quality of life in patients with chronic liver disease. An improvement in quality of life is defined as a significant improvement in the score on the liver-specific quality of life scale compared to the baseline value. |
| Change in insulin sensitivity (HOMA-IR) | from enrollment to the end of treatment at 12 weeks | Insulin sensitivity is assessed using HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), an index that describes the body's resistance to insulin. An improvement is defined as a significant reduction in the HOMA-IR value compared to the baseline value. |
| Changes in the gut microbiome | from enrollment to the end of treatment at 12 weeks | Changes in the gut microbiome (diversity and composition of the microbial population) are investigated using microbiological analyses (e.g. 16S rRNA sequencing). A change is defined as a significant shift in the composition or diversity of the microbiome compared to the baseline value. |
| Reduction of skin AGE | from enrollment to the end of treatment at 12 weeks | Skin AGE (Advanced Glycation End-products) is measured as a biomarker for oxidative stress and skin ageing. A reduction in Skin AGE is defined as a significant decrease in the AGE value compared to the baseline value. |
| Number of participants with selected genetic variants at baseline | baseline | Genotyping will be performed at baseline for the following variants: MBOAT7, TM6SF2, PNPLA3, HSD17B13, and MTARC1. The outcome is defined as the number and proportion of participants carrying each genetic variant. |
| Change in proportion fo circulating immune cell subsets | from enrollment to the end of treatment at 12 weeks | Immunophenotyping will be performed to quantify circulating immune cell subsets, including Th1, Th17, regulatory T cells (Treg), CD4+ T cells, CD8+ T cells, CD16+ cells, naïve and IgA+ B cells, natural killer cells, neutrophils, and M1 and M2 macrophages. The outcome is defined as the mean change in the proportion (%) of each immune cell subset from baseline to Week 12. |
| Change in fasting plasma glucose | From enrollment to end of treatment at 12 weeks | Fasting plasma glucose will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12 |
| Change in LDL cholesterol | From enrollment to end of treatment at 12 weeks. | low-density lipoprotein (LDL) cholesterol will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12. |
| Change in HDL cholesterol | From enrollment to end of treatment at 12 weeks. | High-density lipoprotein (HDL) cholesterol will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12. |
| Change in triglycerides | From enrollment to end of treatment at 12 weeks. | Triglyceride levels will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12. |
| Change in blood pressure | From enrollment to end of treatment at 12 weeks. | Systolic and diastolic blood pressure will be measured in mmHg. The outcome is defined as the mean change from baseline to week 12. |
| Change in serum cytokine and chemokine levels | From enrollment to end of treatment at 12 weeks | Serum levels of cytokines and chemokines, including IL-6, IL-6 receptor, IL-8, CCL2, TNF-α, and IFN-γ, will be measured. The outcome is defined as the mean change in concentration (pg/mL) from baseline to Week 12. |
Countries
Germany
Contacts
CONTACTUte M Stern
PRINCIPAL_INVESTIGATORJörn M Schattenberg, Prof. Dr.
Department of Internal Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
Outcome results
None listed