NASH-FITTER: Nonalcoholic Steatohepatitis Fitness Intervention Treatment Targeting Endothelial Dysfunction Reversal (NASH-FITTER)

This research is being done to find out if aerobic exercise is beneficial in reversing scarring. Physical activity has been shown to increase fitness in healthy individuals as well as in those with NASH. This research will allow for better understanding the effects of physical activity on fitness and endothelial function in patients with NASH with the goal of reversing scarring.

Approximately 12 people will take part in this research study at Penn State (PSU) Milton S. Hershey Medical Center (HMC), Penn State Physical Medicine & Research (PM&R) Laboratories housed at the Hershey Center for Applied Research (HCAR) and the Penn State University Fitness Center (UFC).

Study Overview

• Status: Withdrawn
• Conditions: NASH - Nonalcoholic Steatohepatitis; Non-Alcoholic Fatty Liver Disease; Non Alcoholic Steatohepatitis
• Intervention / Treatment: Behavioral: Moderate intensity aerobic exercise

Detailed Description

Preliminary studies show universally low cardiorespiratory fitness (CRF) in Nonalcoholic steatohepatitis (NASH) patients was dependent on body composition. The proposed work is based on the hypothesis that gains in cardiorespiratory fitness and improved endothelial function achieved through exercise can arrest or reverse progression of hepatic fibrosis, lessen cardiovascular disease risk (CVD), and improve all-cause mortality in patients with NASH. The aims of this research proposal are designed to characterize and better understand the effects of physical activity (PA) on CRF and endothelial function in patients with NASH. The goal is to arrest progression of fibrosis and reduce CVD risk. This proposal includes a cross-sectional study and a small pilot clinical trial in a high-risk subgroup of NASH most likely to benefit from PA.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

•Enrollment and completion of IRB study # 00011797

Exclusion Criteria

• Inability to provide informed consent
• Institutionalized/prisoner
• Non-English-speaking patients due to unavailability of translators for all visits/sessions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Moderate intensity aerobic exercise; All subjects will undergo DXA and CRF measurement (relative VO2max) under the supervision of an American College of Sports Medicine (ACSM)-certified fitness professional and study physician at the Penn State PM&R Research Laboratories. Subjects selected for the interventional pilot trial will receive a FitBit Charge2 HR and be instructed on how to use a FitBit Hear Rate monitor, Fitbit application, Fitbit website, and Fitabase (secure data management platform utilized by >400 clinical trials). Participants will record their daily food and beverage intake through the Fitbit app. Individualized feedback will be provided by a registered dietician (RD). Subjects that meet requirements for the exercise arm (12 total) will be required to exercise 30 minutes, five days per week at a moderate intensity (HR target corresponding to 45-55% of their relative VO2max). Each session will be supervised in-person at the Penn State University Fitness Center with an ACSM certified exercise physiologist.

Behavioral: Moderate intensity aerobic exercise; Subjects that meet requirements for the exercise arm (12 total) will be required to exercise 30 minutes, five days per week at a moderate intensity (HR target corresponding to 45-55% of their relative VO2max). Each session will be supervised in-person at the Penn State University Fitness Center with an ACSM certified exercise physiologist. This is feasible as Zhang et al.(87) found 66 out of 70 subjects (95%) completed the twelve-month supervised in-person moderate-intensity exercise protocol five-days a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hepatic fibrosis stage using METAVIR score	The primary endpoint of this study is change in hepatic fibrosis stage.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fibrosis change and gains in cardiorespiratory fitness	correlation between fibrosis change and gains in CRF	12 months
flow mediated dilation	correlation between fibrosis change and improvements in FMD	12 months
NAFLD Activity Score (NAS)	The diagnosis of nonalcoholic steatohepatitis (NASH) is defined by the presence and pattern of specific histological abnormalities on liver biopsy. A separate system of scoring the features of nonalcoholic fatty liver disease (NA) called the NAFLD Activity Score (NAS) was developed as a tool to measure changes in NAFLD. The grading or NAFLD activity score (NAS) encompasses steatosis, lobular inflammation and ballooning.	12 months
intra-hepatic fat content	changes in intra-hepatic fat content	12 months
health related quality of life (HRQOL)	PROMIS is a computer adaptive test (CATs) used to assess health related quality of life. The survey contains profiles that measure multiple concepts through a fixed collection of short forms.	12 months
Body composition	body composition change	12 months

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Jonathan G Stine, MD, Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2019
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: NAFLD; NASH; fatty liver
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: STUDY00012210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No