Clinical trial NCT04899102: Intermittent Fasting for NAFLD in Adults
Official title: Pilot Study of Time-Restricted, Intermittent Fasting for Non-Alcoholic Fatty Liver Disease in Non-Obese Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fatty Liver
Intermittent Fasting
Fatty Liver, Nonalcoholic
Non-Alcoholic Fatty Liver Disease
Liver Fat
Keywords: Fatty Liver
Intermittent Fasting
Non-obese
Diet
Nutrition
Time-restricted
Liver Fat
Non-Alcoholic Fatty Liver Disease
Fatty Liver, Nonalcoholic
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2021-05-24
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Every individual enrolled will follow a special type of diet for 6 weeks, called time-restricted, intermittent fasting.
Primary purpose: TREATMENT

Brief summary: NAFLD is a growing threat to public health. Currently, there is a significant need for highly effective treatments for NAFLD. Non-obese NAFLD (BMI\<30kg/m2) is an increasingly recognized condition, sometimes described as "lean NAFLD". Intermittent Fasting (IF) may be uniquely beneficial in non-obese NAFLD. The purpose of this study is to identify non-pharmacologic, lifestyle-based methods of NAFLD treatment within non-obese adults.

Detailed description: Nonalcoholic fatty liver disease (NAFLD), which encompasses a spectrum from simple steatosis and steatohepatitis (NASH) to fibrosis and cirrhosis, is the leading cause of liver disease in the United States. There are currently no FDA-approved pharmacologic therapies for NAFLD and NASH, and standard low-calorie diets are often minimally effective, difficult to adhere to and to maintain. Thus, continued investigation of strategies to treat NAFLD and NASH is greatly needed. Non-obese NAFLD (BMI\<30kg/m2) is an increasingly recognized condition, sometimes described as "lean NAFLD". It is estimated that 10-20% of American and Europeans without obesity have this condition. There is a pressing need for the study of lifestyle interventions independent of weight loss to treat this important subset of NAFLD patients. This protocol aims to investigate the utility of time restricted, intermittent fasting (TRF) as a potential method. Adults with non-obese NAFLD are at risk of progression to end-stage liver disease and development of cardiometabolic disease. Intermittent Fasting (IF) may be uniquely beneficial in non-obese NAFLD. IF is characterized by periods of dietary restriction leading to metabolic production and use of ketones from adipocytes rather than hepatically-derived glucose.

The goal of this study is to learn if time-restricted, intermittent fasting can help reduce the amount of fat in the liver in adults with non-alcoholic fatty liver disease (NAFLD). Ideally, this study will yield more information about time-restricted, intermittent fasting as a potential lifestyle-based treatment for adults with NAFLD and a body mass index (BMI) between 23-30 kg/m\^2.

Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide informed consent
2. Age 18 years or older at time of consent
3. BMI 23-30kg/m\^2 at screening
4. Evidence of NAFLD confirmed by historical procedure obtained no more than 6 months prior to the screening visit, defined as:

   * Grade \>=1 steatosis on clinical liver biopsy; OR
   * Fatty liver on validated imaging modality (non-contrast CT scan, MR Spectroscopy, MRI proton density fat fraction, ultrasound)
5. Liver fat fraction ≥10% on H-MRS performed during the screening period
6. Hepatitis C antibody and Hepatitis B surface antigen negative at screening

Exclusion Criteria:

1. Heavy alcohol use for at least 3 consecutive months within the past 5 years prior to screening \[heavy alcohol consumption is defined as: \> 20g daily for women or \> 30mg daily for men, assessed by the Lifetime Drinking History assessment at screening (23, 24)\].
2. Evidence of other known forms of chronic liver disease including:

   • Alcoholic liver disease, hepatitis B, hepatitis C, PBC, PSC, autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (HCC).
3. Current or prior history of Type II Diabetes requiring insulin or sulfonylureas due to risk of hypoglycemia with fasting.
4. Use of any pharmacological treatments for NAFLD/NASH within the 6 months prior to the screening visit, except vitamin E. Patients on a stable dose of vitamin E can be enrolled in the study.
5. Unstable body weight \[defined as: \>10% reduction in body weight in the 6 months prior to the screening visit\]
6. Known cirrhosis, stage 4 fibrosis on prior liver biopsy, or clinical evidence of cirrhosis or portal hypertension on imaging or exam.
7. Current or prior history of Child-Pugh score ≥7.
8. History of liver transplant, or current placement on a liver transplant list.
9. Known positivity for human immunodeficiency virus infection.
10. Prior or planned bariatric surgery, patients on active pharmacological treatment for weight loss, or active involvement in a weight loss program.
11. Routine MRI exclusion criteria, such as the presence of a pacemaker or cerebral aneurysm clip.
12. Chronic Kidney Disease (CKD) with eGFR \< 60.
13. For women of child-bearing potential (WOCBP): positive urine hCG, trying to achieve pregnancy, or breastfeeding \[a negative urine pregnancy test is required at screening for women of child-bearing potential\].
14. Other medical conditions or severe chronic illnesses that, in the opinion of the Investigator, may present a contraindication to study participation.
15. Any other condition that, in the opinion of the Investigator, may hinder study compliance or completion of the study schedule of assessments.

Primary outcomes:
measure: Liver Fat Content
timeFrame: change from baseline to 6 weeks
Secondary outcomes:
measure: ≥30% Relative Liver Fat Reduction Proportion
timeFrame: change from baseline to 6 weeks
measure: Visceral Adipose Tissue Content
timeFrame: change from baseline to 6 weeks
measure: Quality of Life Score
timeFrame: change from baseline to 6 weeks
measure: Dietary Intake
timeFrame: change from baseline to 6 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References: