AzTrials
AzTrials

Liver DiseasesNCT03518294

NASH Fitness Intervention in Thrombosis Trial (NASHFit)

A study testing Aerobic Exercise in people with Liver Diseases and Blood Disorder, run by Milton S. Hershey Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Aerobic Exercise
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
1 Jun 2018to 24 Mar 2021
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Penn State Hershey Medical Center

    Hershey, Pennsylvania, 17033

Other trials in United States

About this study

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.

Read the 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.

Being tested
Aerobic Exercise
Keywords
NAFLD, NASH
Medical subject headings
Liver Diseases, Hematologic Diseases, Digestive System Diseases, Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aerobic ExerciseBehavioural

    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.

Study groups in NCT03518294
Study groupRoleWhat they receive
Standard of CareNo interventionSubjects 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.
Aerobic ExerciseExperimentalSubjects 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.
Receives: Behavioral: Aerobic Exercise

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PAI-1 Level

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

    Measured: 5 months

Secondary outcomes (11)

  1. Change in Von Williebrand Factor (vWF)

    Change in vWF was calculated by taking the difference of measurements at baseline and 5 months.

    Measured: 5 months

  2. Change in Protein S

    Change in protein S was calculated by taking the difference of measurements at baseline and 5 months.

    Measured: 5 months

  3. Change in Factor VIII

    Change in factor VIII was calculated by taking the difference of measurements at baseline and 5 months.

    Measured: 5 months

  4. Change in Fibrinogen

    Change in fibrinogen was calculated by taking the difference of measurements at baseline and 5 months.

    Measured: 5 months

  5. Change in Antithrombin

    Change in antithrombin was calculated by taking the difference of measurements at baseline and 5 months.

    Measured: 5 months

  6. Change in Protein C

    Change in protein C was calculated by taking the difference of measurements at baseline and 5 months.

    Measured: 5 months

  7. Change in Adiponectin

    Change in adipontin was calculated by taking the difference of measurements at baseline and 5 months.

    Measured: 5 months

  8. Patatin Like Phospholipase-3 (PNPLA3) rs738409 Polymorphism

    Patatin like phospholipase-3 (PNPLA3) rs738409 polymorphism genotyping subjects (GG, GC and CC genotypes)

    Measured: 5 months

  9. Change in PAI-1 Stratified by Fibrosis Stage

    Change is the difference between measurements at baseline and 5 months

    Measured: 5 months

  10. Change in % Hepatic Fat

    Change in % hepatic fat was calculated by taking the difference of measurements at baseline and 5 months.

    Measured: 5 months

  11. Health Related Quality of Life (HRQOL) Change

    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.

    Measured: 5 months (20 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2018
  2. Study start1 Jun 2018
  3. Primary completion24 Mar 2021
  4. Study completion24 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Standard of care Aerobic exercise
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03518294
Sponsor's protocol ID
8507
Status last verified
Jan 2023
First submitted
23 Apr 2018
Last updated
3 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Channapragada T, Batra S, Hummer BL, Chinchilli VM, Huang D, Loomba R, Schreibman IR, Stine JG. Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index. Dig Dis Sci. 2026 Feb;71(2):628-635. doi: 10.1007/s10620-025-09361-9. Epub 2025 Sep 3.

    PubMed 40900364

  • Cuthbertson DJ, Keating SE, Pugh CJA, Owen PJ, Kemp GJ, Umpleby M, Geyer NG, Chinchilli VM, Stine JG. Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease. Liver Int. 2024 Sep;44(9):2368-2381. doi: 10.1111/liv.15947. Epub 2024 Jun 7.

    PubMed 38847589

  • Harris SJ, Smith N, Hummer B, Schreibman IR, Faust AJ, Geyer NR, Chinchilli VM, Sciamanna C, Loomba R, Stine JG. Exercise training improves serum biomarkers of liver fibroinflammation in patients with metabolic dysfunction-associated steatohepatitis. Liver Int. 2024 Feb;44(2):532-540. doi: 10.1111/liv.15769. Epub 2023 Nov 28.

    PubMed 38014619

  • Motz V, Faust A, Dahmus J, Stern B, Soriano C, Stine JG. Utilization of a Directly Supervised Telehealth-Based Exercise Training Program in Patients With Nonalcoholic Steatohepatitis: Feasibility Study. JMIR Form Res. 2021 Aug 17;5(8):e30239. doi: 10.2196/30239.

    PubMed 34402795

Questions about this trial

What is this clinical trial studying?

A study testing Aerobic Exercise in people with Liver Diseases and Blood Disorder, run by Milton S. Hershey Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PAI-1 Level (time frame: 5 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03518294, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in