Clinical trial NCT05220956: Impact of Time-restricted Feeding in NAFLD
Official title: Impact of Time-restricted Feeding on Hepatic Steatosis in NAFLD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fatty Liver Disease
Fatty Liver
Fatty Liver, Nonalcoholic
Keywords: liver fibrosis
time restricted feeding
Lead sponsor: Johannes Gutenberg University Mainz
Sponsor class: OTHER
Collaborators: name: University of Turin, Italy
First posted: 2022-02-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomised controlled study with NAFLD-patients. One arm will undergo a TRF diet (Time-Restricted Feeding) for 12 weeks. The control arm is not subject to any time restrictions concerning eating.
Primary purpose: SCREENING

Brief summary: This is a randomised controlled study of patients with Non-Alcoholic Fatty Liver Disease (NAFLD).

Patients will be trained according to the 10 rules of a healthy nutrition according to the German Association for Nutrition (DGE).

One arm will undergo Time-Restricted Feeding (TRF) for 12 weeks. The control arm is not subject to any time restrictions concerning eating.

It will be investigated whether TRF improves insulin sensitivity, impacts on metabolic inflammation and reduces liver steatosis.

Detailed description: Patients are recruited in the Liver Outpatient Clinic of the University Medical Center of Mainz.

About 100 patients will be enrolled in this pilot study. Inclusions criteria are exclusions of known causes of liver injury, Body Mass Index (BMI) \> 25 kg/m\^2, severe steatosis according to CAP ≥ 300 dB/m and absence of advanced fibrosis according to liver stiffness \< 13 kPa.

Following the written consent, all patients will be trained to undertake a 2-week lead-in period of DGE.

Beginning in week 3 (Visit 2), an interventional group and a control group are generated through randomisation. The interventional group is instructed to follow TRF, whereas the control group is not subject to any time restrictions. Both arms will be accompanied for a duration of 12 weeks.TRF diet is based on temporal food consumption between 8:00 a.m. and 16:00 p.m., thus a 16 hour lasting period. After 10 weeks from the completion of the experimental phase (wash-out period), there will be the "end of follow up" visit.

The whole duration of the study is 24 weeks (2 weeks lead-in, 12 weeks intervention and 10 weeks post-intervention investigation).

Transient elastography (Fibroscan) is conducted at the screening visit, randomization visit, and at weeks 8, end of treatment visit and end of study visit. Spleen stiffness measurement is performed at randomization visit, week 8 and end of treatment visit. There will be 5 visits at the study center (screening, randomization, week 8, end of treatment and end of study) and 2 phone visits (week 6 and week 12). At each visit clinical events, body weight and standard laboratory parameters, identification of the CAP and stiffness values will be collected. Participants will fill in questionnaires capturing quality of life. At randomization visit and end of treatment visit, an OGTT will be performed to assess insulin sensitivity.

Adverse events will be recorded. Phone visits are used to survey the safety of patients.

Non-adherence to TRF for 2 days per week (20% of the total study period) has been selected as cut off to define treatment failure at per-protocol analysis.

Eligibility criteria: Patients with steady medication during the last 3 months. A diabetes mellitus must not be decompensated (HbA1c \<6.5%). Patients with advanced fibrosis - defined about the non-invasive Fibroscan-procedure (Fibroscan \>13 kPa) - will not be included.

Complete inclusion criteria:

1. Age between 18 and 75 years
2. Body Mass Index (BMI) \> 25 kg/m2
3. Grade 3 steatosis evaluated by with CAP ≥ 300 dB/m and exclusion of known causes of liver steatosis
4. Liver elastography \< 13 kPa
5. Capability to understand the study and the individual consequences of participation
6. Signed and dated declaration of agreement in the forefront of the study

Complete exclusion criteria:

1. Liver cirrhosis
2. Hepatocellular carcinoma or non-curative treated carcinoma
3. Alcohol consumption \>20g (female) und \>30 g (male)/day
4. Other causes of chronic liver disease (HBV, HCV, HDV, HEV, HIV), autoimmune diseases or chronic cholestatic liver disease, hereditary haemochromatosis, Wilson disease, α-1-Antitrypsin deficiency
5. Medications which cause liver disease or secondary NAFLD (e. g. Tamoxifen, systemic Corticosteroids, Methotrexate, Tetracycline, Estrogens, Valproic acid)
6. Changes in body weight \> 5% in the last 6 months
7. Statins and/ or other fat-reducer medications if not taken in steady dosage during at least 4 weeks
8. Uncontrolled diabetes type 2 defined as HbA1c value \> 9.0% or insulin depending type 2 diabetes
9. Pregnancy
10. Immunologic or inflammatory disease (e. h. systemic lupus erythematodes)
11. Patients after organ transplantations
12. Missing or lacking consent capability

Primary outcomes:
measure: Evaluation of the impact of TRF on liver steatosis by CAP (dB/m)
timeFrame: 12 weeks
Secondary outcomes:
measure: Changes in liver fibrosis by liver stiffness (kPa) under TRF
timeFrame: 12 weeks
measure: Changes in FIB-4 as indirect non-invasive tools of liver fibrosis
timeFrame: 12 weeks
measure: Evaluation of changes in direct non-invasive tool of liver fibrosis ELF
timeFrame: 12 weeks
measure: Evaluation of changes in direct marker of liver fibrogenesis PRO-C3 (ng/ml)
timeFrame: 12 weeks
measure: Evaluation of changes in liver-specific quality of life
timeFrame: 12 weeks
measure: Evaluation of changes in insulin sensitivity
timeFrame: 12 weeks
measure: Evaluation of changes in the gut microbiota
timeFrame: 12 weeks
measure: Evaluation of changes in markers of oxidative stress (AGEs)
timeFrame: 12 weeks
measure: Changes in spleen volume by spleen stiffness under TRF
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: University Medical Center of the Johannes Gutenberg Univeristy
state: Rheinland-Pfalz
Study officials:
affiliation: 1. Medical Department
name: Jörn M. Schattenberg, Prof.
role: PRINCIPAL_INVESTIGATOR
References: