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NASH Fitness Intervention in Thrombosis Trial (NASHFit)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03518294
Recruitment Status : Completed
First Posted : May 8, 2018
Results First Posted : February 3, 2023
Last Update Posted : February 3, 2023
Sponsor:
Information provided by (Responsible Party):
Jonathan Stine, 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.

Condition or disease Intervention/treatment Phase
Liver Diseases Blood Disorder Digestive System Disease Behavioral: Aerobic Exercise Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Standard of care Aerobic exercise
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NASH Fitness Intervention in Thrombosis Trial (NASHFit)
Actual Study Start Date : June 1, 2018
Actual Primary Completion Date : March 24, 2021
Actual Study Completion Date : March 24, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Clots

Arm Intervention/treatment
No Intervention: Standard of Care
Subjects in the control condition will be instructed to continue their medical care at the discretion of their treating medical professional. They will be informed to maintain their current physical activity level. Weekly phone calls will be performed by study personnel to ensure adherence to the protocol (no changes in activity). Subjects will report to Penn State on a monthly basis for anthropometric assessment to confirm their self-reports and study investigators will perform and interim history and physical examination at that time.
Experimental: 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.
Behavioral: 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 :
  1. PAI-1 Level [ Time Frame: 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 :
  1. Change in Von Williebrand Factor (vWF) [ Time Frame: 5 months ]
    Change in vWF was calculated by taking the difference of measurements at baseline and 5 months.

  2. Change in Protein S [ Time Frame: 5 months ]
    Change in protein S was calculated by taking the difference of measurements at baseline and 5 months.

  3. Change in Factor VIII [ Time Frame: 5 months ]
    Change in factor VIII was calculated by taking the difference of measurements at baseline and 5 months.

  4. Change in Fibrinogen [ Time Frame: 5 months ]
    Change in fibrinogen was calculated by taking the difference of measurements at baseline and 5 months.

  5. Change in Antithrombin [ Time Frame: 5 months ]
    Change in antithrombin was calculated by taking the difference of measurements at baseline and 5 months.

  6. Change in Protein C [ Time Frame: 5 months ]
    Change in protein C was calculated by taking the difference of measurements at baseline and 5 months.

  7. Change in Adiponectin [ Time Frame: 5 months ]
    Change in adipontin was calculated by taking the difference of measurements at baseline and 5 months.

  8. Patatin Like Phospholipase-3 (PNPLA3) rs738409 Polymorphism [ Time Frame: 5 months ]
    Patatin like phospholipase-3 (PNPLA3) rs738409 polymorphism genotyping subjects (GG, GC and CC genotypes)

  9. Change in PAI-1 Stratified by Fibrosis Stage [ Time Frame: 5 months ]
    Change is the difference between measurements at baseline and 5 months

  10. Change in % Hepatic Fat [ Time Frame: 5 months ]
    Change in % hepatic fat was calculated by taking the difference of measurements at baseline and 5 months.

  11. Health Related Quality of Life (HRQOL) Change [ Time Frame: 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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria Adults age >=18 or <70 years Liver biopsy <= 6months prior to enrollment Biopsy proven NASH(79)

Lack of secondary causes of hepatic fat accumulation:

Significant alcohol consumption (<21 drinks/week for men and <14 drinks/week for women) Chronic hepatitis C Wilson disease Lipodystrophy Parenteral nutrition Long-term use of steatogenic medications (mipomersen, lomitapide, amiodarone, methotrexate, tamoxifen, corticosteroids) Monogenic hereditary disorders

Exclusion Criteria >90 minutes/week of at least moderate intensity exercise over the previous three months Pregnancy BMI <18 or >40 kg/m2(16) Uncontrolled diabetes (changes in medication dosing over the previous three months or hemoglobin A1c >9%)(12) Active cardiac symptoms Severe medical comorbidities/psychiatric illness Decompensated cirrhosis (history of esophageal varices, ascites or hepatic encephalopathy) Abdominal hernia Cancer with life expectancy <6 months MRI contraindications (severe claustrophobia, implanted ferrous metal) Other liver disease (positive hepatitis B surface antigen, antinuclear antibody titer >1:160) Active weight-loss program participation or weight-loss supplement use Active substance abuse/smoking Inability to provide informed consent Institutionalized/prisoner Inability to walk > 2 blocks or ¼ mile. Physical Activity Readiness Questionnaire (PAR-Q) score >=1 at the discretion of the study PI


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03518294


Locations
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United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
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Principal Investigator: Jonathan Stine, MD Milton S. Hershey Medical Center
  Study Documents (Full-Text)

Documents provided by Jonathan Stine, Milton S. Hershey Medical Center:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jonathan Stine, Assistant Professor Medicine, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT03518294    
Other Study ID Numbers: 8507
First Posted: May 8, 2018    Key Record Dates
Results First Posted: February 3, 2023
Last Update Posted: February 3, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jonathan Stine, Milton S. Hershey Medical Center:
NAFLD
NASH
Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases
Gastrointestinal Diseases
Thrombosis
Hematologic Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases