Exercise for Liver Cirrhosis

Overseen By Annette Bellar

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Must not be taking: Corticosteroids, Anticoagulants

Disqualifiers: Active alcohol use, Liver transplant, Active malignancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different types of exercise might benefit people with liver cirrhosis, a condition that impairs liver function and leads to muscle loss and other health issues. Participants will be divided into groups to try either endurance exercises, like cycling, or resistance exercises, like weight lifting, to determine which is more beneficial. Those diagnosed with cirrhosis and free from alcohol and drugs for at least six months might be suitable candidates. The aim is to determine whether exercise can improve muscle mass and overall health for those living with this condition. As an unphased trial, this study offers participants the chance to contribute to valuable research that could enhance the quality of life for those with liver cirrhosis.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that affect muscle protein turnover, like corticosteroids, or medications used to prevent clotting. If you are on these medications, you may need to stop them to participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that people with cirrhosis can safely engage in endurance exercises, especially for up to 12 weeks. These activities are well-tolerated and can improve heart health and reduce fatigue.

For resistance exercises, the findings are less clear. Some studies have mixed results, but many report no harmful effects. In fact, resistance training can enhance physical fitness and quality of life for those with liver cirrhosis without causing harm. It is important to remember that while endurance exercise is generally safe, the safety of resistance exercise might differ from person to person. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these exercise-based treatments for liver cirrhosis because they offer a non-pharmaceutical approach to managing the condition. Unlike traditional treatments that rely on medication to slow liver damage or manage symptoms, endurance training and resistance exercise aim to improve liver health by enhancing overall fitness and muscle strength. This could potentially lead to better quality of life and physical function for patients. Additionally, these exercise regimens may reduce the need for medication, minimizing side effects and improving patient adherence.

What evidence suggests that this trial's treatments could be effective for cirrhosis?

This trial will compare different exercise interventions for liver cirrhosis. Research has shown that endurance exercise, which participants in the Endurance Arm of this trial may receive, benefits people with liver cirrhosis. It improves muscle mass, strength, physical function, and quality of life without causing harm. Meanwhile, resistance exercise, which participants in the Resistance Arm may receive, builds muscle strength and size in people with cirrhosis, enhancing physical fitness and overall well-being. Both types of exercise provide a safe way to manage symptoms and improve health in cirrhosis. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 40-65 with cirrhosis who haven't drunk alcohol or used recreational drugs in the last 6 months. They should have a Child's score of 5-10, MELD score under 21, and no severe illnesses or medications that affect muscle mass. People with advanced heart/lung disease, recent heavy drinking, certain medication use, active cancer/infection/ascites/encephalopathy, poor clotting ability, end-stage kidney disease or those unlikely to complete the study are excluded.

Inclusion Criteria

I am between 40 and 65 years old.

My liver function score is between 5 and 10.

I don't have illnesses or take medications that affect my muscle mass, diabetes, or use blood thinners.

Exclusion Criteria

I have had a liver transplant.

I am not taking steroids or blood clot prevention drugs.

Active alcohol consumption within 6 weeks of enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-baseline

Participants undergo a maximal exercise/fitness test and body composition measurements

1 week

1 visit (in-person)

Treatment

Participants engage in 12 weeks of either endurance or resistance exercise

12 weeks

Weekly supervised exercise sessions

Follow-up

Participants complete a final fitness test to examine the effects of de-training

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Endurance Training
• Resistance Exercise
• Standard of Care

Trial Overview The study tests how resistance (strength-building) exercise twice weekly and endurance (cardiovascular health-promoting) training thrice weekly for 12 weeks affect patients with liver cirrhosis compared to standard care. It looks at changes in muscle mass and ammonia processing due to exercise by measuring fitness levels at different intervals.

How Is the Trial Designed?

Group I: Resistance Experimental Treatment 1 Intervention

Group II: Endurance Arm Experimental Treatment 1 Intervention

Group III: Standard of Care Active Control 1 Intervention

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

Progressive resistance training (PRT) is shown to significantly improve muscle strength in individuals with multiple sclerosis (MS), based on a systematic review of 16 studies.

While PRT shows positive trends in improving functional capacity, balance, and self-reported measures like fatigue and quality of life, the evidence is less robust, indicating a need for more focused research on these outcomes and the underlying mechanisms involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple sclerosis and progressive resistance training: a systematic review. Kjølhede, T., Vissing, K., Dalgas, U.[2022]

Exercise training for cirrhotic patients awaiting liver transplants is safe and can significantly improve their physical capacity and frailty scores, with no reported adverse events related to the exercise programs.

Regular exercise, particularly a combination of aerobic and resistance training, has been associated with reduced readmission rates and improved survival outcomes for patients post-transplant, highlighting the importance of tailored exercise prescriptions in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training as an intervention for frailty in cirrhotic patients on the liver transplant waiting list: A systematic review. Loschi, TM., Baccan, MDTA., Della Guardia, B., et al.[2023]

Exercise can be beneficial for patients with cirrhosis, leading to improvements in metabolic profile, quality of life, muscle mass, and cardiopulmonary function, especially after programs lasting more than 14 weeks.

While exercise may initially increase hepatic venous pressure gradient (HVPG), long-term exercise programs can actually decrease HVPG, making exercise a promising intervention for managing cirrhosis, though it should be tailored to individual patient needs and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise prescription in patients with cirrhosis: Recommendations for clinical practice. Macías-Rodríguez, RU., Ruiz-Margáin, A., Román-Calleja, BM., et al.[2021]

A 3-week exercise program using a whole body vibration platform significantly improved muscle strength in patients with multiple sclerosis, particularly in the quadriceps and hamstrings, compared to a control group.

While the exercise program enhanced muscle strength, it did not lead to significant improvements in functional mobility, as measured by balance and walking tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 3 weeks' whole body vibration training on muscle strength and functional mobility in hospitalized persons with multiple sclerosis. Claerbout, M., Gebara, B., Ilsbroukx, S., et al.[2012]

Patients with cirrhosis show significantly reduced exercise capacity and muscle strength compared to healthy individuals, which may impact their outcomes during liver transplantation.

Improving exercise capacity through training is well tolerated in cirrhosis patients and may enhance post-transplant survival, suggesting that pretransplant physical conditioning could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise capacity and muscle strength in patients with cirrhosis. Jones, JC., Coombes, JS., Macdonald, GA.[2022]

The study evaluated the feasibility of multimodal agility-based exercise training (MAT) for people with multiple sclerosis (pwMS) and found that both MAT and traditional strength and endurance training (SET) were feasible in an inpatient setting, with participants completing the required number of sessions.

While both groups showed similar short-term reductions in fatigue and improvements in motor function, MAT participants demonstrated a significant improvement in walking endurance, exceeding the minimal important change, suggesting potential benefits of MAT for pwMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal agility-based exercise training (MAT) versus strength and endurance training (SET) to improve multiple sclerosis-related fatigue and fatigability during inpatient rehabilitation: a randomized controlled pilot and feasibility study [ReFEx]. Wolf, F., Nielsen, J., Saliger, J., et al.[2023]

An 8-week home-based exercise training (HET) program for cirrhosis patients was found to be safe and effective, leading to significant improvements in peak aerobic power (peak VO2) and 6-minute walk distance (6MWD).

Patients who adhered to the program (completing ≥80% of sessions) experienced even greater benefits, highlighting the importance of exercise adherence for maximizing improvements in exercise capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home Exercise Training Improves Exercise Capacity in Cirrhosis Patients: Role of Exercise Adherence. Kruger, C., McNeely, ML., Bailey, RJ., et al.[2019]

In a review of six randomized clinical trials involving 173 participants with cirrhosis, physical exercise did not show a clear beneficial or harmful effect on mortality, morbidity, or health-related quality of life, suggesting that more research is needed in this area.

While there were no deaths in the exercise group compared to two in the control group, the evidence regarding serious adverse events and physical fitness improvements was low quality, indicating that the safety and efficacy of exercise for people with cirrhosis remain uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical exercise for people with cirrhosis. Aamann, L., Dam, G., Rinnov, AR., et al.[2022]

A systematic review of 20 randomized controlled trials involving exercise training in individuals with multiple sclerosis showed that exercise significantly improves muscular fitness (small effect size of 0.27) and cardiorespiratory fitness (moderate effect size of 0.47).

The results indicate that while exercise training leads to beneficial changes in fitness levels for people with MS, the improvements in muscular fitness are smaller compared to those in cardiorespiratory fitness, highlighting the importance of exercise in rehabilitation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Exercise Training on Fitness in Multiple Sclerosis: A Meta-Analysis. Platta, ME., Ensari, I., Motl, RW., et al.[2022]

In a pilot study involving 19 patients with cirrhosis, 8 weeks of supervised aerobic exercise significantly improved peak oxygen uptake (peak VO2) by 5.3 mL/kg/min compared to a control group, indicating enhanced exercise capacity.

The exercise program also led to increased thigh muscle thickness and circumference, improved self-perceived health status, and reduced fatigue, all without any adverse effects during the training, suggesting that aerobic exercise is safe and beneficial for patients with cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eight weeks of exercise training increases aerobic capacity and muscle mass and reduces fatigue in patients with cirrhosis. Zenith, L., Meena, N., Ramadi, A., et al.[2022]

Exercise training is highly beneficial for patients with cirrhosis, leading to significant improvements in muscle health, quality of life, and functional capacity, without any reported adverse events.

The authors advocate for routine exercise prescriptions in cirrhosis care, providing clinicians with practical tools and resources to implement exercise programs effectively in various healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in cirrhosis: Translating evidence and experience to practice. Tandon, P., Ismond, KP., Riess, K., et al.[2019]

In a study of 18 patients with liver cirrhosis, the combination of L-carnitine supplementation and increased physical activity significantly improved daily step counts and serum carnitine levels over 6 months.

While muscle strength and volume did not show significant changes, L-carnitine treatment reduced the frequency of muscle cramping, suggesting it may help manage muscle complications in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can L-carnitine supplementation and exercise improve muscle complications in patients with liver cirrhosis who receive branched-chain amino acid supplementation? Hiraoka, A., Kiguchi, D., Ninomiya, T., et al.[2020]

Progressive resistance training (PRT) is a safe and effective short-term intervention for people with relapsing-remitting multiple sclerosis, leading to increased muscle strength, endurance, and reduced physical fatigue after 10 weeks of training.

Despite improvements in strength and quality of life, PRT did not result in better walking performance, and the benefits were not sustained after the training period ended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial. Dodd, KJ., Taylor, NF., Shields, N., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7311690/

Exercise and physical activity in cirrhosis: opportunities or perils Endurance exercise for up to 12 wk is clinically tolerated in well-compensated cirrhosis. Data on the safety of resistance exercise are conflicting. Nutritional ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S180759322500167X

Review articles Effect of aerobic and resistance training on ... Aerobic and resistance physical training appear to improve the QoL and functional capacity without changing body composition in patients with liver cirrhosis.

3. journals.lww.com journals.lww.com/md-journal/fulltext/2025/08220/advanced_exercise_intervention_for_liver_cirrhosis.30.aspx

Advanced exercise intervention for liver cirrhosis and... Preliminary validation demonstrated its effectiveness in improving muscle mass, strength, physical function, and quality of life. 1.

4. mdpi.com mdpi.com/2072-6643/16/15/2532

Impact of Physical Activity on Overall Survival and Liver ... This study investigates the relationship between physical activity and liver-related outcomes with or without steatotic liver diseases.

5. cghjournal.org cghjournal.org/article/S1542-3565%2814%2900604-1/fulltext

Eight Weeks of Exercise Training Increases Aerobic ... Patients with cirrhosis have reduced exercise tolerance, measured objectively as decreased peak exercise oxygen uptake (peak VO2).

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35973182/

A Systematic Review of Randomized Clinical Trials A review of 11 RCTs with 358 participants with advanced liver disease demonstrates that exercise interventions can have favorable outcomes ...

7. journals.lww.com journals.lww.com/md-journal/fulltext/2018/10190/exercise_as_an_intervention_for_patients_with.28.aspx

Exercise as an intervention for patients with end-stage liver ... In all of the studies reviewed, there was no harm documented by any cirrhotic patients who underwent exercise while there was potential benefit in endurance ...