Impact of Time-restricted Feeding in NAFLD

Fatty Liver Clinical Trial

— NAFLD-TRF  

Official title:

Impact of Time-restricted Feeding on Hepatic Steatosis in NAFLD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05220956
• Other study ID #: 21-00784
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2021
• Est. completion date: December 1, 2024

Study information

• Verified date: December 2023
• Source: Johannes Gutenberg University Mainz
• Contact: Jörn M. Schattenberg, Prof.
• Phone: 06131-17
• Email: joern.schattenberg[@]unimedizin-mainz.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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, a-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

Related Conditions & MeSH terms

• Fatty Liver
• Fatty Liver Disease
• Fatty Liver, Nonalcoholic
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

Behavioral:
• Intermittent fasting
One arm will undergo a TRF diet (Time-Restricted Feeding) for 12 weeks while both arms undergo a training according to the 10 rules of healthy nutrition of the DGE.
• DGE diet
The control arm is not a subject to any time restrictions concerning eating while both arms undergo a training according to the 10 rules of healthy nutrition of the DGE.

Locations

Country	Name	City	State
Germany	University Medical Center of the Johannes Gutenberg Univeristy	Mainz	Rheinland-Pfalz

Sponsors (2)

Lead Sponsor	Collaborator
Johannes Gutenberg University Mainz	University of Turin, Italy

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the impact of TRF on liver steatosis by CAP (dB/m)	The primary outcome of interest is a change in CAP value of a least 20 db/m with TRF	12 weeks
Secondary	Changes in liver fibrosis by liver stiffness (kPa) under TRF	Liver elastography performed as surrogate marker of liver fibrosis	12 weeks
Secondary	Changes in FIB-4 as indirect non-invasive tools of liver fibrosis	Changes in the surrogate marker of liver fibrosis FIB-4	12 weeks
Secondary	Evaluation of changes in direct non-invasive tool of liver fibrosis ELF	Performed as surrogate markers of liver fibrosis	12 weeks
Secondary	Evaluation of changes in direct marker of liver fibrogenesis PRO-C3 (ng/ml)	Performed as surrogate markers of liver fibrosis	12 weeks
Secondary	Evaluation of changes in liver-specific quality of life	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.	12 weeks
Secondary	Evaluation of changes in insulin sensitivity	Changes in insulin sensitivity by indexes derived by HOMA-IR score	12 weeks
Secondary	Evaluation of changes in the gut microbiota	Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis.	12 weeks
Secondary	Evaluation of changes in markers of oxidative stress (AGEs)	AGEs as surrogate markers of oxidative stress	12 weeks
Secondary	Changes in spleen volume by spleen stiffness under TRF	Spleen stiffness performed as surrogate of spleen volume	12 weeks