Recruitment

Recruitment Status
Enrolling by invitation
Estimated Enrollment
Same as current

Summary

Conditions
  • Non Alcoholic Fatty Liver Disease
  • Obesity
  • Pre Diabetes
Type
Interventional
Phase
Not Applicable
Design
Allocation: RandomizedIntervention Model: Parallel AssignmentMasking: Single (Outcomes Assessor)Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 65 years
Gender
Both males and females

Description

Background: 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. Alternate day fasting (ADF) has been ...

Background: 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. Alternate day fasting (ADF) has been shown in animals to reduce hepatic steatosis and improve hepatic insulin sensitivity, but these findings have yet to be confirmed in human subjects. ADF consists of a "feast day" where individuals are permitted to consume food ad libitum, alternated with a "fast day" where individuals consume 25% of their usual intake (~500 kcal). We performed a pilot study to evaluate the effects of ADF combined with exercise, versus ADF or exercise alone, on hepatic parameters in prediabetic patients. Our results show that the combination of ADF plus exercise produced greater reductions in alanine aminotransferase (ALT; an indirect marker of hepatic steatosis), compared to ADF alone, or exercise alone, after 12 weeks. Greater decreases in insulin resistance, HbA1c, LDL cholesterol, and more pronounced increases in HDL cholesterol, were observed in the combination group versus individual interventions. Data from our pilot trial also suggest that these decreases in insulin resistance may be mediated in part by changes in hepatocyte-derived hormones (hepatokines) that occur with liver fat reduction. Although these pilot findings are very promising, these data still require confirmation by a well powered longer-term (24 week) clinical trial. Hypotheses: The present proposal will test the following hypotheses: (1) The combination group (ADF plus exercise) will experience greater reductions in hepatic steatosis (measured by magnetic resonance spectroscopy; MRS) when compared to ADF or exercise alone; (2) The combination group will experience greater improvements in hepatokine profile (fetuin-A, fetuin B, FGF-21, RBP4, selenoprotein P, SHBG, adropin) when compared to ADF or exercise alone; (3) The combination group will experience greater improvements in hepatic insulin sensitivity, insulin resistance and HbA1c and other metabolic disease risk variables (fasting glucose, fasting insulin, triglycerides, LDL cholesterol, blood pressure, inflammatory parameters) when compared to ADF or exercise alone. Methods: To test these objectives, a 24-week randomized, controlled, parallel-arm feeding trial will be implemented. Obese prediabetic individuals with NAFLD (n = 360) will be randomized to 1 of 4 groups: (1) ADF (fast day: 25% energy intake, feed day: ad libitum fed, no exercise), (2) exercise (ad libitum fed, training 5 days/week supervised), (3) combination (ADF plus exercise), and (4) control (ad libitum fed, no exercise). Significance: If the aims of this application are achieved, this study will be the first to show that the combination of alternate day fasting plus aerobic exercise is an effective non-pharmacological therapy to reduce hepatic steatosis, improve hepatic insulin sensitivity and prevent the progression of prediabetes to type 2 diabetes in NAFLD patients.

Tracking Information

NCT #
NCT04004403
Collaborators
Not Provided
Investigators
Principal Investigator: Krista Varady, PhD University of Illinois Chicago