NASH Fitness Intervention in Thrombosis Trial (NASHFit)
Condition: Liver Diseases; Blood Disorder; Digestive System Disease
MeSH terms: Liver Diseases; Digestive System Diseases; Gastrointestinal Diseases; Thrombosis; Hematologic Diseases
Study type: Interventional

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.
    

Intervention name(s): Aerobic Exercise
Intervention type(s): Behavioral
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Standard of care Aerobic exercise
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: NAFLD; NASH