Alternate Day Fasting, Exercise, and NAFLD

Obesity Clinical Trial

Official title:

Alternate Day Fasting Combined With Exercise for the Treatment of Non-alcoholic Fatty Liver Disease (NAFLD)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04004403
• Other study ID #: 2019-0300
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 1, 2019
• Est. completion date: May 1, 2024

Study information

• Verified date: November 2023
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Approximately 65% of obese individuals have non-alcoholic fatty liver disease (NAFLD), and this condition is strongly related to the development of insulin resistance and diabetes. Innovative lifestyle strategies to treat NAFLD are critically needed. The proposed research will demonstrate that alternate day fasting (ADF) combined with exercise is an effective non-pharmacological therapy to treat NAFLD.

Description:

Nonalcoholic fatty liver disease (NAFLD) is characterized by an accumulation of fat in the liver (not resulting from excessive alcohol consumption). Approximately 65% of obese individuals have NAFLD, and this condition is strongly related to the development of insulin resistance and type 2 diabetes. While certain pharmacological agents have been shown to reduce liver fat (i.e. thiazolidinediones), there is mounting concern regarding the safety and weight-gaining effects of these compounds. In light of this, recent research has focused on non-pharmacological lifestyle therapies to reduce hepatic steatosis, such as daily calorie restriction combined with aerobic exercise. Evidence from clinical trials suggest that this combination is an effective lifestyle therapy improve liver fat content and hepatic insulin sensitivity. More recently, it's been shown that intermittent fasting may produce even greater improvements in hepatic steatosis and hepatic insulin sensitivity, when compared to conventional calorie restriction. For instance, intrahepatic lipid accumulation was lower and insulin sensitivity was higher in mice fasted every other day, when compared to mice who were energy restricted every day. Moreover, data from human trials show that adults with obesity experience greater decreases in insulin and insulin resistance with intermittent fasting versus daily restriction. These findings suggest that intermittent fasting may be a more effective diet therapy to reduce hepatic steatosis and improve insulin sensitivity, when compared to daily calorie restriction. Although these findings are very promising, these data still require confirmation by a randomized controlled clinical trial.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: May 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

INCLUSION CRITERIA:

• Age between 18 to 65 years old
• BMI between 30.0 and 59.9 kg/m2
• NAFLD (hepatic steatosis = 5% confirmed by MRI-PDFF)
• Sedentary (<20 min, 2x/week of light activity at 3-4 metabolic equivalents (METs) for 3 mo prior to study)

EXCLUSION CRITERIA:

• Have chronic liver disease other than NAFLD (hepatitis B or C, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, a1-antitrypsin deficiency)
• Consume excessive amounts of alcohol women: 70 g of ethanol (5 alcoholic drinks per week) and men 140 g of ethanol (10 drinks per week) in the past 6 months)
• Have a history of known cardiovascular, pulmonary or renal disease
• Diagnosed T1DM or T2DM
• Are not weight stable for 3 months prior to the beginning of study (weight gain or loss > 4 kg)
• Are claustrophobic or have implanted metallic/electrical devices (e.g. cardiac pacemaker, neuro-stimulator)
• Are taking drugs that induce steatosis (e.g. corticosteroids, estrogens, methotrexate, Ca channel blockers)
• Are taking drugs that benefit NAFLD (e.g. betaine, pioglitazone, rosiglitazone, metformin, or gemifibrozil)
• Are taking drugs that influence study outcomes (weight loss medications)
• Are perimenopausal or have an irregular menstrual cycle (menses that does not appear every 27-32 days)
• Are pregnant, or trying to become pregnant
• Are smokers

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Obesity

Intervention

Other:
• Alternate day fasting
The diet involves consuming 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days".
• Exercise
The exercise intervention involves supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax.

Locations

Country	Name	City	State
United States	University of Illinois Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in hepatic steatosis	Hepatic steatosis will be measured by magnetic resonance imaging (MRI-PDFF)	Change from week 1 to week 12
Secondary	Change in body weight	Measured by digital scale	Change from week 1 to week 12
Secondary	Change in lean mass	Measured by dual-energy x-ray absorptiometry (DXA)	Change from week 1 to week 12
Secondary	Change in fat mass	Measured by dual-energy x-ray absorptiometry (DXA)	Change from week 1 to week 12
Secondary	Change in visceral fat mass	Measured by dual-energy x-ray absorptiometry (DXA)	Change from week 1 to week 12
Secondary	Change in Alanine Aminotransferase (ALT)	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Secondary	Change in Aspartate Aminotransferase (AST)	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Secondary	Change in fasting glucose	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Secondary	Change in fasting insulin	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Secondary	Change in insulin sensitivity	Measured by Quantitative insulin sensitivity check index (QUICKI)	Change from week 1 to week 12
Secondary	Change in insulin resistance	Measured by Homeostatic model assessment (HOMA)	Change from week 1 to week 12
Secondary	Change in plasma lipid levels	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Secondary	Change in HbA1c	Measured by a commercial lab (Medstar, Inc)	Change from week 1 to week 12
Secondary	Change in blood pressure	Measured by a blood pressure cuff	Change from week 1 to week 12
Secondary	Change in heart rate	Measured by a blood pressure cuff	Change from week 1 to week 12
Secondary	Dietary intake	Measured by a 7-day food record	Change from week 1 to week 12
Secondary	Physical activity	Measured by an activity monitor (Fitbit Alta)	Change from week 1 to week 12
Secondary	Hepatokine - Fetuin-A (ng/ml)	Measured by ELISA	Change from week 1 to week 12
Secondary	Hepatokine - FGF-21 (ng/ml)	Measured by ELISA	Change from week 1 to week 12
Secondary	Hepatokine - Selenoprotein P (ng/ml)	Measured by ELISA	Change from week 1 to week 12
Secondary	Sleep quality and duration	Measured by Pittsburgh Sleep Quality Index (PSQI). The PSQI is a 19-item self-report questionnaire that measures sleep quality in the past month, resulting in a total score of 0-21. Scores above 5 indicate poor sleep quality.	Change from week 1 to week 12
Secondary	Insonmia severity	Measured by the Insomnia Severity Index (ISI). The ISI is a 7-item self-report questionnaire that rates each item by a 5-point Likert scale, resulting in a total score of 0-28. Scores are stratified into the following categories: no clinically significant insomnia (0-7); subthreshold insomnia (8-14); moderate severity insomnia (15-21); and severe insomnia (22-28).	Change from week 1 to week 12
Secondary	Risk of obstructive sleep apnea	Measured using the 10-item self-report Berlin Questionnaire which estimates % occurrences of sleep apnea	Change from week 1 to week 12