Clinical trial NCT06664684: Intermittent Fasting and Metabolic Dysfunction Associated Fatty Liver Disease
Official title: Effects of Intermittent Fasting in Metabolic Dysfunction Associated Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intermittent Fasting
Metabolic Dysfunction-Associated Fatty Liver Disease
Keywords: Intermittent fasting
fibroblast growth factor 21
autophagy
fatty liver
time-restricted eating
Lead sponsor: Istanbul Bilgi University
Sponsor class: OTHER
Collaborators: name: Marmara University
First posted: 2024-10-29
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Previous studies have investigated the effect of different dietary patterns on metabolic dysfunction-associated fatty liver disease (MAFLD), for which lifestyle modification remains the primary treatment. The present study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers including autophagy-related protein (ATG)-5 and BECLIN-1 levels, as well as on hepatic steatosis and fibrosis levels in overweight or obese patients with MAFLD to elucidate the efficacy of intermittent fasting in the management of MAFLD. The study included 48 patients diagnosed with MAFLD. Patients were randomly assigned into two groups: 22 received a dietary treatment involving 22-25 kcal/kg/day of energy for 8 weeks (energy-restricted diet group), and 26 followed the same dietary intervention and a 16:8 pattern (energy + time-restricted diet group). The patients were assessed for various parameters at baseline (T0) and at the end of the week 8 (T8). The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan® device. Serum levels of FGF-21, BECLIN-1, and ATG-5 were determined using enzyme-linked immunosorbent assay.


Eligibility criteria: Inclusion Criteria:

* Diagnosed with MAFLD
* Aged 18-65 years
* BMI ≥ 25 kg/m²
* A stable body weight (\<5 kg weight loss or gain) over the last 3 months preceding the start of the study
* Signed the informed consent form.

Exclusion Criteria:

* An average daily alcohol consumption \>20 g for females and \>30 g for males
* Pregnant or lactating women
* Patients with ischemic heart disease or heart failure, chronic inflammatory diseases, chronic viral infections, cancer, moderate-to-severe kidney disease, uncontrolled hypertension, and eating disorders
* Those with a history of bariatric surgery
* Those on insulin due to increased risk of hypoglycemia.

Primary outcomes:
measure: Transient elastography
timeFrame: Measurements were taken twice before and 8 weeks after the intervention.
Secondary outcomes:
measure: Serum FGF-21
timeFrame: Measurements were taken twice before and 8 weeks after the intervention.
measure: Serum ATG-5
timeFrame: Measurements were taken twice before and 8 weeks after the intervention.
measure: Serum BECLIN-1
timeFrame: Measurements were taken twice before and 8 weeks after the intervention.
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Institute of Gastroenterology, Liver Research Unit, Marmara University
Study officials:
References:
citation: Czaja MJ. Function of Autophagy in Nonalcoholic Fatty Liver Disease. Dig Dis Sci. 2016 May;61(5):1304-13. doi: 10.1007/s10620-015-4025-x. Epub 2016 Jan 2.
citation: Itoh N. FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases. Front Endocrinol (Lausanne). 2014 Jul 7;5:107. doi: 10.3389/fendo.2014.00107. eCollection 2014.
citation: Kleinert M, Muller TD. A New FGF21 Analog for the Treatment of Fatty Liver Disease. Diabetes. 2020 Aug;69(8):1605-1607. doi: 10.2337/dbi20-0025. No abstract available.
citation: Byun S, Seok S, Kim YC, Zhang Y, Yau P, Iwamori N, Xu HE, Ma J, Kemper B, Kemper JK. Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase. Nat Commun. 2020 Feb 10;11(1):807. doi: 10.1038/s41467-020-14384-z.
citation: Hydes TJ, Ravi S, Loomba R, E Gray M. Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH. Clin Mol Hepatol. 2020 Oct;26(4):383-400. doi: 10.3350/cmh.2020.0067. Epub 2020 Jul 17.
citation: Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020 May;158(7):1999-2014.e1. doi: 10.1053/j.gastro.2019.11.312. Epub 2020 Feb 8.