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Impact of Time-restricted Feeding in NAFLD

Not Applicable
Recruiting
Conditions
Fatty Liver Disease
Fatty Liver
Fatty Liver, Nonalcoholic
Interventions
Behavioral: DGE diet
Behavioral: Intermittent fasting
Registration Number
NCT05220956
Lead Sponsor
Johannes Gutenberg University Mainz
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DGE dietDGE dietThis control arm is not a subject to any time restrictions concerning eating, solely patients will be trained according to the 10 rules of healthy nutrition of the DGE.
Intermittent fastingIntermittent fastingThis arm will undergo a TRF diet (Time-Restricted Feeding) for 12 weeks.
Primary Outcome Measures
NameTimeMethod
Evaluation of the impact of TRF on liver steatosis by CAP (dB/m)12 weeks

The primary outcome of interest is a change in CAP value of a least 20 db/m with TRF

Secondary Outcome Measures
NameTimeMethod
Evaluation of changes in the gut microbiota12 weeks

Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis.

Evaluation of changes in markers of oxidative stress (AGEs)12 weeks

AGEs as surrogate markers of oxidative stress

Changes in spleen volume by spleen stiffness under TRF12 weeks

Spleen stiffness performed as surrogate of spleen volume

Evaluation of changes in insulin sensitivity12 weeks

Changes in insulin sensitivity by indexes derived by HOMA-IR score

Changes in FIB-4 as indirect non-invasive tools of liver fibrosis12 weeks

Changes in the surrogate marker of liver fibrosis FIB-4

Evaluation of changes in liver-specific quality of life12 weeks

Evaluation of Patient Reported Outcomes using the Chronic Liver Disease Questionnaire (CLDQ). The CLDQ uses 29 items in four domains, each scored on a Likert scale from 1 (all of the time) to 7 (none of the time) representing the frequency of clinical symptoms and emotional problems in the last two weeks. Results are reported in the six subscale scores (abdominal symptoms, fatigue, systemic symptoms, activity, emotional functioning, worry) and a CLDQ overall score.

Changes in liver fibrosis by liver stiffness (kPa) under TRF12 weeks

Liver elastography performed as surrogate marker of liver fibrosis

Evaluation of changes in direct non-invasive tool of liver fibrosis ELF12 weeks

Performed as surrogate markers of liver fibrosis

Evaluation of changes in direct marker of liver fibrogenesis PRO-C3 (ng/ml)12 weeks

Performed as surrogate markers of liver fibrosis

Trial Locations

Locations (1)

University Medical Center of the Johannes Gutenberg Univeristy

🇩🇪

Mainz, Rheinland-Pfalz, Germany

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