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

Trial Summary

What is the purpose of this trial?

There is no known cure or regulatory agency approved drug therapy for nonalcoholic fatty liver disease (NAFLD), the leading cause of liver disease worldwide, and its progressive type, NASH. This places increased importance on using exercise to treat NAFLD. While physical activity is recommended for all with NAFLD, how to best prescribe exercise as a specific treatment remains unknown, including what dose of exercise is most effective.

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 data supports the effectiveness of the treatment for non-alcoholic fatty liver disease?

Research shows that high-intensity interval training (HIIT) can improve liver health and reduce risk factors for non-alcoholic fatty liver disease (NAFLD) in obese adults. Even a short amount of HIIT each week can lead to better liver function and overall health improvements. ^{1 2 3 4 5}

Is high-intensity interval training safe for humans?

High-intensity interval training (HIIT) has been studied in people with non-alcoholic fatty liver disease and is generally considered safe. It can improve liver health, heart function, and overall fitness without significant adverse effects. ^{1 2 4 5 6}

How does high-intensity interval training differ from other treatments for non-alcoholic fatty liver disease?

High-intensity interval training (HIIT) is unique because it is a time-efficient exercise method that can significantly reduce liver fat and improve heart function in people with non-alcoholic fatty liver disease. Unlike other treatments, HIIT involves short bursts of intense exercise followed by rest, making it an effective option for those with limited time. ^{1 2 4 6 7}

Research Team

Jonathan G Stine, MD

Principal Investigator

Milton S. Hershey Medical Center

Eligibility Criteria

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

I am between 18 and 69 years old.

My liver has mild to moderate scarring.

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

Exclusion Criteria

AUDIT-C questionnaire identified significant alcohol use

Substance abuse/active smoking

My diabetes is not well-controlled.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The effect of low volume sprint interval training in patients with non-alcoholic fatty liver disease. [2018]

2. United States 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. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of exercise on the development of new fatty liver and the resolution of existing fatty liver. [2018]

4. Germany 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. [2022]

5. Poland 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. [2022]

6. England 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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