Time-restricted Feeding in MASLD (MASLD-Interval)

The Impact of Time-restricted Feeding on Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)

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.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Associated-dysfunction Steatotic Liver Disease (MASLD)
• Intervention / Treatment: Behavioral: time-restricted feeding in a 5:2 regimen

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ute M Stern; Phone Number: + 49 6841 16 15863; Email: ute.stern@uni-saarland.de

Study Locations

• Germany
  • Saarland
    • Homburg, Saarland, Germany, 66424
      • Recruiting
      • Department of Internal Medicine II, Saarland University Medical Center, Saarland University,
      • Contact: Ute M Stern; Phone Number: +49 6841 16 15863; Email: ute.stern@uni-saarland.de
      • Sub-Investigator: Maurice Michel, Dr.

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5:2 fasting; Participants in this arm are advised to follow a 5:2 intermittent fasting regimen. On two non-consecutive days per week, their energy intake is restricted to a maximum of one-quarter of their individual requirements (approximately 500-600 kcal). On these fasting days, participants are encouraged to consume only breakfast and then fast until the following morning. On the remaining five days, they are advised to follow a healthy, balanced diet in line with the recommendations of the German Nutrition Society (DGE), without specific (caloric) restrictions.	Behavioral: time-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).
No Intervention: control group; The control group follows a balanced diet without fasting, based on the DGE guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of controlled attenuation parameter (CAP)	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	from enrollment to the end of treatment at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in liver stiffness measurment (LSM)	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.	from enrollment to the end of treatment at 12 weeks
Improvement in CLDQ-NAFLD/NASH for liver-specific quality of life	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.	from enrollment to the end of treatment at 12 weeks
Change in insulin sensitivity (HOMA-IR)	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.	from enrollment to the end of treatment at 12 weeks
Changes in the gut microbiome	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.	from enrollment to the end of treatment at 12 weeks
Reduction of skin AGE	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.	from enrollment to the end of treatment at 12 weeks
Number of participants with selected genetic variants at 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.	baseline
Change in proportion fo circulating immune cell subsets	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.	from enrollment to the end of treatment at 12 weeks
Change in fasting plasma glucose	Fasting plasma glucose will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12	From enrollment to end of treatment at 12 weeks
Change in LDL cholesterol	low-density lipoprotein (LDL) cholesterol will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12.	From enrollment to end of treatment at 12 weeks.
Change in HDL cholesterol	High-density lipoprotein (HDL) cholesterol will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12.	From enrollment to end of treatment at 12 weeks.
Change in triglycerides	Triglyceride levels will be measured in mg/dL. The outcome is defined as the mean change from baseline to week 12.	From enrollment to end of treatment at 12 weeks.
Change in blood pressure	Systolic and diastolic blood pressure will be measured in mmHg. The outcome is defined as the mean change from baseline to week 12.	From enrollment to end of treatment at 12 weeks.
Change in serum cytokine and chemokine levels	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.	From enrollment to end of treatment at 12 weeks

Collaborators and Investigators

• Sponsor: Universität des Saarlandes
• Collaborators: 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
• Investigators: Principal Investigator: Jörn M Schattenberg, Prof. Dr., Department of Internal Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): May 15, 2029
• Study Completion (Estimated): May 15, 2029

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: nutrition; lifestyle intervention; dietary intervention; time-restricted feeding; MASLD; steatotic liver disease; intermittend fasting; 5:2 fasting; liver health
• Additional Relevant MeSH Terms: Behavior; Feeding Behavior; Fasting; Intermittent Fasting; Health Care Quality, Access, and Evaluation; Therapeutics; Health Care Evaluation Mechanisms; Quality of Health Care; Epidemiologic Study Characteristics; Clinical Protocols
• Other Study ID Numbers: 100/25

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No