High-Intensity Interval Training for Non-alcoholic Fatty Liver Disease

(AMPED Trial)

Overseen By Breianna L Hummer, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Milton S. Hershey Medical Center

Disqualifiers: Active cardiac symptoms, Cancer, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how exercise can help treat non-alcoholic fatty liver disease (NAFLD), as no approved cure currently exists. Researchers aim to determine the best type and amount of exercise for individuals with this condition. Participants will either follow a specific exercise routine or receive advice based on current best practices. Suitable candidates have NAFLD, have been sedentary (less than 90 minutes of exercise a week), and have a body mass index (BMI) over 25. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research that could shape future exercise recommendations for NAFLD.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on exercise as a treatment for liver disease.

What prior data suggests that this exercise regimen is safe for individuals with NAFLD?

Research has shown that High-Intensity Interval Training (HIIT) is safe and well-tolerated for individuals with nonalcoholic fatty liver disease (NAFLD) and its more advanced form, NASH. Studies have found that HIIT not only boosts fitness levels but also significantly reduces liver fat. Participants in these studies did not report any major side effects, making HIIT a promising way to improve liver health. Additionally, HIIT has been shown to enhance insulin use in the body, benefiting overall health. For those considering joining a trial with HIIT, current evidence suggests it is a safe choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using high-intensity interval training (HIIT) for non-alcoholic fatty liver disease (NAFLD) because it offers a non-pharmacological approach that could complement or even improve upon standard care, which usually involves lifestyle changes and sometimes medications to manage liver health. Unlike traditional treatments, HIIT is an exercise protocol that can be done in-person or virtually, making it highly accessible. This method emphasizes short, intense bursts of aerobic activity, such as walking or jogging, with specific regimens of 750 or 1,000 MET-minutes per week, potentially making it more engaging and sustainable for patients. Additionally, HIIT may enhance cardiovascular fitness and metabolic health more efficiently than standard moderate exercise, providing added benefits beyond liver health.

What evidence suggests that exercise might be an effective treatment for NAFLD?

Research has shown that high-intensity interval training (HIIT) can reduce liver fat and improve liver health in individuals with non-alcoholic fatty liver disease (NAFLD). One study found that aerobic exercise decreased liver fat by 21% in just four weeks. In this trial, participants in the exercise arms will engage in aerobic activities, such as walking, jogging, or using cardio equipment. HIIT has also significantly lowered liver fat, body mass index (BMI), and liver enzymes like ALT and AST, which indicate liver health. Another study reported a 16.6% reduction in liver fat after HIIT. These findings suggest that regular high-intensity workouts could effectively manage NAFLD. ^{2 3 4 5 6}

Who Is on the Research Team?

Christopher Sciamanna, MD

Principal Investigator

Milton S. Hershey Medical Center

Are You a Good Fit for This Trial?

The AMPED trial is for adults aged 18-69 with a BMI over 30 who are mostly inactive and have been diagnosed with NASH, a type of liver disease. They must have had a liver biopsy within the last six months showing specific levels of liver damage. People can't join if they're very overweight (BMI >45), have heart problems, other liver diseases, severe health issues, drink too much alcohol or use drugs.

Inclusion Criteria

My liver has mild to moderate scarring.

My liver condition is confirmed by specific tests to be severe.

Sedentary [<90 min/wk of exercise identified by the Get Active Questionnaire (GAQ)

Exclusion Criteria

AUDIT-C questionnaire identified significant alcohol use

Substance abuse/active smoking

My diabetes is not well-controlled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in aerobic exercise with varying doses (750 MET-min/wk or 1,000 MET-min/wk) for 3-5 days per week, 22-60 minutes per session at moderate to vigorous intensity.

16 weeks

Sessions can be completed in person or virtually

Follow-up

Participants are monitored for changes in liver fat, fibrosis, and other health markers after the treatment phase.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise

Trial Overview This study looks at how different amounts of exercise can help treat non-alcoholic fatty liver disease (NAFLD) since there's no approved drug treatment yet. It aims to find out what 'dose' of exercise works best for patients with NAFLD.

How Is the Trial Designed?

Group I: Exercise Arm 2 Experimental Treatment 1 Intervention

Aerobic exercise will be completed by walking, jogging or running or by using cardio equipment (e.g., recumbent bike). Each session will begin with a warm-up with walking and dynamic exercises. A 5-min walking cool down will end the session. The training dose for this arm is 1,000 MET-min/wk for 3-5 days per week, 30-60 minutes per session at a moderate to vigorous intensity. The exercise can be completed in person or virtually.

Group II: Exercise Arm 1 Experimental Treatment 1 Intervention

Aerobic exercise will be completed by walking, jogging or running or by using cardio equipment (e.g., recumbent bike). Each session will begin with a warm-up with walking and dynamic exercises. A 5-min walking cool down will end the session. The training dose for this arm is 750 MET-min/wk for 3-5 days per week, 22-45 minutes per session at a moderate to vigorous intensity. The exercise can be completed in person or virtually.

Group III: Standard of Care Active Control 1 Intervention

This group will receive best NASH clinical practices counseling at baseline and end-of-trial in accordance with NAFLD clinical practice guidelines and be reinforced by handouts from the American Liver Foundation.

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Published Research Related to This Trial

Sprint interval exercise training (SIT) is feasible for men with non-alcoholic fatty liver disease (NAFLD), with participants completing over 96% of the prescribed intervals during the 6-week study.

SIT led to a significant reduction in intrahepatic triglyceride (IHTG) by 12.4% and visceral adipose tissue (VAT) by 16.9%, demonstrating its potential effectiveness in improving liver health without requiring weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sprint interval training on ectopic lipids and tissue-specific insulin sensitivity in men with non-alcoholic fatty liver disease. Sargeant, JA., Bawden, S., Aithal, GP., et al.[2022]

Both high intensity interval training (HIIT) and moderate intensity continuous exercise training (MICT) effectively reduced intrahepatic lipid (IHL) content in obese adults with nonalcoholic fatty liver disease (NAFLD), with HIIT showing a 37% reduction and MICT a 20% reduction over 4 weeks.

The study found that the reductions in IHL were not significantly different between HIIT and MICT, suggesting that both exercise intensities can be beneficial for NAFLD without necessarily leading to changes in body weight or abdominal fat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Energy-matched moderate and high intensity exercise training improves nonalcoholic fatty liver disease risk independent of changes in body mass or abdominal adiposity - A randomized trial. Winn, NC., Liu, Y., Rector, RS., et al.[2018]

In a study of 23 adults with non-alcoholic fatty liver disease (NAFLD), modified high-intensity interval training (HIIT) for 12 weeks significantly reduced liver fat from 11% to 8% and whole-body fat mass from 35 kg to 33 kg, compared to no change in the control group.

HIIT also improved cardiac function, as indicated by an increase in the early diastolic filling rate, while showing no significant differences in glucose control, suggesting that HIIT can be an effective part of NAFLD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomized controlled trial. Hallsworth, K., Thoma, C., Hollingsworth, KG., et al.[2022]

A 6-week low-volume sprint interval training (SIT) protocol did not show significant improvements in liver function or other health markers in patients with non-alcoholic fatty liver disease (NAFLD), despite initial benefits observed during a control period.

While some measures like walking speed and blood pressure improved during the control phase, these benefits did not enhance further with the SIT intervention, suggesting that this specific exercise regimen may not be effective for managing NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of low volume sprint interval training in patients with non-alcoholic fatty liver disease. MacLean, C., Dillon, J., Babraj, JA., et al.[2018]

In a study of 233,676 individuals over 5 years, exercising at least 5 times a week significantly reduced the risk of developing new fatty liver disease, with a hazard ratio of 0.86, indicating a 14% lower risk compared to those who did not exercise.

For individuals with existing fatty liver, engaging in regular exercise (≥5 times per week) was associated with a 40% higher likelihood of resolution of liver fat, with a hazard ratio of 1.40, highlighting the importance of physical activity in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercise on the development of new fatty liver and the resolution of existing fatty liver. Sung, KC., Ryu, S., Lee, JY., et al.[2018]

A 12-week high-intensity interval training (HIIT) program requiring only 28 minutes per week significantly improved liver fibrosis scores and cardiometabolic health in obese patients with metabolic syndrome, compared to a control group that did not exercise.

While both the HIIT and control groups lost weight, only the HIIT group showed significant improvements in liver health, glycemic control, and cardiorespiratory fitness, highlighting the effectiveness of short-duration, high-intensity exercise in managing non-alcoholic fatty liver disease and metabolic syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low-volume interval training improves nonalcoholic fatty liver disease fibrosis score and cardiometabolic health in adults with obesity and metabolic syndrome. Reljic, D., Konturek, PC., Herrmann, HJ., et al.[2022]

High-intensity interval training (HIIT) is an effective and time-efficient exercise therapy for treating non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease and linked to serious health risks.

HIIT has been shown to reduce fat mass, visceral fat, and intrahepatic lipid levels, while also improving liver stiffness, making it a promising option for patients with limited time for exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on Interval Exercise Interventions for Non-Alcoholic Fatty Liver Disease. Hamasaki, H.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10412696/

High-intensity Interval Training for the Management of ... We explored the experiences and perspectives of both professionally supervised and self-directed HIIT in people with NASH and evaluated participant-reported ...

2. nature.com nature.com/articles/s41598-024-51470-4

Effect of different exercise modalities on nonalcoholic fatty ... It has been found that AT can reduce visceral adipose tissue volume by 12% and liver fat content by 21% over a 4-week period. High intensity ...

3. journals.lww.com journals.lww.com/eurojgh/fulltext/2025/07000/effect_of_high_intensity_interval_training_on.1.aspx

Effect of high-intensity interval training on clinical... This study supports the idea that HIIT can significantly reduce IHL, BMI, ALT, and AST levels, and further studies are needed to assess the long-term adherence.

4. eglj.springeropen.com eglj.springeropen.com/articles/10.1186/s43066-022-00229-5

Comparison of the effects of high-intensity interval training and ... The data in Table 1 shows that the body weight increased significantly with fatty liver induction, but training significantly decreased it (P < ...

5. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1032164/full

Does aerobic exercise reduce NASH and liver fibrosis in ... Moreover, Oh et al. (42) reported a reduction of hepatic fat after both HIIT and RT interventions of -16.6% and -47.2%, respectively. Also, Winn ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36538276/

High-Intensity Interval Training is Safe, Feasible and ... Conclusions: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH.