Non-Alcoholic Fatty Liver Disease
Conditions
Brief summary
This study will assess the impact of time-restricted eating (8 hours of eating each day) with standard of care lifestyle recommendations (hypocaloric, Mediterranean diet and 30 minutes of exercise on at least 5 days/week) on the degree of fat in the liver as measured by magnetic resonance imaging.
Detailed description
Time-Restricted Eating (TRE) is a form of caloric restriction through daily prolonged fasting that has been shown to lead to weight loss, improved glucose regulation, and suppression of inflammation. Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is a metabolic condition that in certain patients can lead to significant morbidity and mortality. The only current treatment for MASLD is weight loss. In the proposed study, the investigators aim to test the hypothesis that TRE will add additional benefit in the treatment of MASLD on top of standard of care diet and lifestyle modifications.
Interventions
BEHAVIORALTRE plus SOC
Participants will undergo time restricted eating (TRE) each day for 12 weeks and will be given lifestyle recommendations with respect to diet (500-1000 kcal) and moderate-intensity exercise (30 minutes).
BEHAVIORALSOC
Participants will be given lifestyle recommendations with respect to diet (500-1000 kcal) and moderate-intensity exercise (30 minutes).
BEHAVIORALTRE
Participants will undergo time restricted eating (TRE) each day for 12 weeks plus 4 extra visits with the registered dietician and repeat Fibroscan, InBody composition scan, and MRI-PDFF.
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This is a single-site, randomized, controlled pilot study. The investigators hypothesize that time-restricted eating (TRE) will lead to an additional improvement in hepatic steatosis as compared to standard of care lifestyle recommendations alone measured by MRI-PDFF. The investigators plan to enroll 40 participants to two arms between the years of 18 and 65 with MASLD as defined by MRI-PDFF score of greater or equal to 10%. Participants on the experimental arm (TRE plus SOC) will be required to fast for 16 hours each day for 12 weeks. Counseling will involve instructing the participant to choose an 8-hour eating window. During the fasting window, the participant is able to drink water and black coffee or tea. Participants in both arms will be given lifestyle recommendations with respect to diet and exercise. The RD will instruct participants regarding standard of care lifestyle recommendations, which includes education of a low-calorie diet and moderate-intensity exercise.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Age ≥ 18 and \< 65 years old * Must provide signed written informed consent and agree to comply with the study protocol * BMI \>25 kg/m² * Baseline liver fat content of at least 10% as measured by MRI-PDFF
Exclusion criteria
* Unclear etiology of liver disease * Competing etiologies for hepatic steatosis * Co-existing causes of chronic liver disease according to standard diagnostic testing including, but not restricted to: * Positive hepatitis B surface antigen * Positive hepatitis C virus RNA * Suspicion of drug-induced liver disease * Alcoholic liver disease * Autoimmune hepatitis * Wilson's disease * Hemochromatosis * Primary biliary cholangitis or primary sclerosing cholangitis * Known or suspected hepatocellular carcinoma * Current or recent history (\<5 years) of significant alcohol consumption. For men, significant consumption is defined as \>30g of alcohol per day. For women, it is defined as \>20g of alcohol per day. * Compensated and decompensated cirrhosis (clinical and/or histologic evidence of cirrhosis). NASH patients with fibrosis stage = 4 according to the NASH CRN fibrosis staging system are excluded. * Reduction in weight by ≥ 5% within the prior 90 days * Current fasting for ≥ 12 hours per day on the majority of days each week * Pregnant females * Mental instability or incompetence, such that the validity of the informed consent or ability to be compliant with the study is uncertain * Inability to perform MRI-PDFF and/or study as defined below * Inability to medically perform prolonged fasting (i.e. insulin regimen)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Achieve At Least 30% Reduction in Liver Fat at 12 Weeks | 12 weeks | Evaluate the percentage of patients with baseline MASLD (MRI-PDFF greater than or equal to 10%) who achieve clinically significant improvement in hepatic fat, as defined by greater than or equal to 30% reduction from baseline liver fat on MRI-PDFF, while adopting a time-restricted eating pattern (fasting 16 hours per day) along with standard of care management as compared to patients with only standard of care NAFLD management. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change from Baseline in Liver Stiffness on Fibroscan® at 12 weeks | Baseline, 12 weeks | Evaluate the mean change in liver stiffness as measured by (FibroScan®) from baseline to 12 weeks. |
| Mean Change from Baseline in Quality of Life Score on SF-36 at 12 weeks | Baseline, 12 weeks | Evaluate the mean change of quality of life score from SF-36 from baseline to 12 weeks. Scores range from 0-100. Higher scores indicate better health status, while lower scores indicate a poorer health status. A mean score of 50 has been articulated as the normative value of all scales. |
| Mean Change from Baseline in Weight at 12 weeks | Baseline, 12 weeks | — |
| Mean Change from Baseline in Body Composition Measurements at 12 weeks | Baseline, 12 weeks | Evaluate the mean change of body composition measurements as measure by InBody Body |
| Mean Change from Baseline in aspartate transglutaminase at 12 weeks | Baseline, 12 weeks | Evaluate the mean change in aspartate transglutaminase from baseline to 12 weeks. |
| Mean Change from Baseline in alanine transglutaminase at 12 weeks | Baseline, 12 weeks | Evaluate the mean change in alanine transglutaminase from baseline to 12 weeks. |
| Mean Change from Baseline in total bilirubin at 12 weeks | Baseline, 12 weeks | Evaluate the mean change in total bilirubin from baseline to 12 weeks. |
| Mean Change from Baseline in direct bilirubin at 12 weeks | Baseline, 12 weeks | Evaluate the mean change direct bilirubin from baseline to 12 weeks. |
| Mean Change from Baseline in albumin at 12 weeks | Baseline, 12 weeks | Evaluate the mean change in albumin from baseline to 12 weeks. |
| Mean Change from Baseline in BMI at 12 weeks | Baseline, 12 weeks | Evaluate the mean change of body mass index from baseline to 12 weeks. |
| Mean Change from Baseline in total protein at 12 weeks | Baseline, 12 weeks | Evaluate the mean change in total protein from baseline to 12 weeks. |
Countries
United States
Contacts
CONTACTSonal Kumar, MD
CONTACTLara Phipps
PRINCIPAL_INVESTIGATORSonal Kumar, MD
Weill Medical College of Cornell University
Outcome results
None listed