NASH Fitness Intervention in Thrombosis Trial (NASHFit)

Not Applicable

Completed

Conditions: Liver Diseases
Blood Disorder
Digestive System Disease

Interventions: Behavioral: Aerobic Exercise

Registration Number: NCT03518294

Lead Sponsor: Milton S. Hershey Medical Center

Brief Summary: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States. The most advanced forms of NAFLD are associated with increased liver-related mortality and lower overall survival. The current standard of care for NAFLD is lifestyle changes through diet and exercise. The human genome and regulation of gene expression is influenced by physical activity. NAFLD is a prothrombotic state with derangements in all three phases of hemostasis leading to clinically important clotting events. Exercise can improve coagulation in healthy persons. In this proposal, we seek to begin a line of work to answer the question "Can lifestyle changes effectively mitigate the increased risk of clotting in patients with NAFLD?" focusing initially on the at-risk population genetically susceptible to advanced disease.

Detailed Description: Often comorbid with obesity, nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States affecting 75-100 million adults, of which 15-20 million have the more severe variant nonalcoholic steatohepatitis (NASH). Conservative estimates project a doubling in NASH by 2025.The most advanced forms of NAFLD are associated with increased liver-related mortality and lower overall survival. The most effective treatment for NAFLD remains adopting healthy dietary and exercise patterns, however NAFLD patients are among the least physically active individuals. Predicting exercise behavior on an individual level is highly complex due to differing motivation, physiologic response to and subjective experience of exercise as well as emerging genetic evidence. The human genome and regulation of gene expression is influenced by physical activity. Patatin like phospholipase-3 (PNPLA3) rs738409 polymorphism (GG, GC and CC genotypes) plays a crucial role in the development of NAFLD. The GG genotype is both associated with advanced NAFLD, and predicts response to physical activity. Patients with NASH have extensive extrahepatic disease and are hypercoagulable. NASH is a prothrombotic state with fibrinolytic dysfunction through elevated plasminogen activator inhibitor (PAI-1), an independent risk factor for venous thromboembolism (VTE). Consequently, patients with NASH are predisposed to VTE; the risk of portal vein thrombosis (PVT) in NASH is 210% greater than in other liver disease. NASH patients are also at increased risk for pulmonary embolism (PE) and deep vein thrombosis (DVT).The most advanced forms of NASH have the greatest thrombotic risk. While studies observe that change in diet, weight and physical activity patterns improve NASH, it is not clear whether these lifestyle changes also reduce the elevated clot risk, however, moderate-intensity exercise leads to improved fibrinolysis in healthy persons.The NASHFit study is being done to find out if exercise is beneficial in decreasing the risk of clotting problems in patients with NASH. Exercise has been shown to decrease markers of clotting in healthy individuals as well as in those with cardiovascular disease.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aerobic Exercise	Aerobic Exercise	Subjects in the aerobic exercise group will be supervised to exercise 30 minutes, 5 times per week at a moderate intensity. Formal exercise instruction and supervision will be provided by ACSM certified fitness professionals at the Penn State University Fitness Center. Aerobic exercise can be completed on either the treadmill, exercise bike, rowing machine or the elliptical machine.

Primary Outcome Measures

Name	Time	Method
PAI-1 Level	5 months	Change in fibrinolysis as indicated by PAI-1 level was calculated by taking the difference of measurements at baseline and 5 months.

Secondary Outcome Measures

Name	Time	Method
Change in Von Williebrand Factor (vWF)	5 months	Change in vWF was calculated by taking the difference of measurements at baseline and 5 months.
Change in Fibrinogen	5 months	Change in fibrinogen was calculated by taking the difference of measurements at baseline and 5 months.
Change in Factor VIII	5 months	Change in factor VIII was calculated by taking the difference of measurements at baseline and 5 months.
Change in PAI-1 Stratified by Fibrosis Stage	5 months	Change is the difference between measurements at baseline and 5 months
Change in Antithrombin	5 months	Change in antithrombin was calculated by taking the difference of measurements at baseline and 5 months.
Patatin Like Phospholipase-3 (PNPLA3) rs738409 Polymorphism	5 months	Patatin like phospholipase-3 (PNPLA3) rs738409 polymorphism genotyping subjects (GG, GC and CC genotypes)
Health Related Quality of Life (HRQOL) Change	5 months (20 weeks)	Data was collected at baseline and at 5 months to assess changes in domains of health. PROMIS-29 Profile v2.1 (Physical function \& pain interference) PROMIS Bank v2.0 - Instrumental Support (Social Support) Scores are reported as standardized T-score metrics derived from population means, with a mean of 50 and standard deviation of 10. The minimum is 0 and the maximum is 90. A higher score for fatigue, pain intensity, pain interference, sleep disturbance, anxiety and depression means a worse outcome. A higher score for physical function and social roles means a better outcome.
Change in Protein S	5 months	Change in protein S was calculated by taking the difference of measurements at baseline and 5 months.
Change in Adiponectin	5 months	Change in adipontin was calculated by taking the difference of measurements at baseline and 5 months.
Change in % Hepatic Fat	5 months	Change in % hepatic fat was calculated by taking the difference of measurements at baseline and 5 months.
Change in Protein C	5 months	Change in protein C was calculated by taking the difference of measurements at baseline and 5 months.