HMB + Amino Acids for Liver Cirrhosis

Overseen By Annette Bellar

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Must not be taking: Muscle metabolism drugs, Blood thinners

Disqualifiers: Recent bleeding, Infection, Encephalopathy, others

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

Compensation: Varies

Number of Visits: 1

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find a treatment for muscle loss in people with liver cirrhosis, a severe liver disease. Researchers are testing whether a mix of hydroxymethyl butyrate (HMB) and amino acids can help regain muscle mass. Participants may receive either HMB or a balanced amino acid mixture to determine which is more effective. People with liver cirrhosis who have stable liver function and haven't experienced recent complications might be good candidates for this trial. As an unphased study, this trial offers participants the opportunity to contribute to groundbreaking research that could lead to new treatments for muscle loss.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that alter muscle protein metabolism or interfere with blood clotting.

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

Research shows that hydroxymethyl butyrate (HMB) is generally safe. Studies have found that HMB can be taken without major side effects and might even help lower heart-related risks. In people with liver cirrhosis, early research suggests HMB could improve muscle health, although some studies did not find noticeable changes in muscle mass or function.

Regarding the balanced amino acid mixture, evidence indicates that amino acid supplements, like branched-chain amino acids (BCAAs), are often used for liver cirrhosis. They are usually well-tolerated and can aid in protein processing, which is important for muscle health. However, some people might experience mild side effects, such as digestive issues.

Overall, both HMB and the amino acid mix appear safe, with no major side effects reported in studies. However, participants should consider any personal health conditions or allergies before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Hydroxy Methyl Butyrate (HMB) for liver cirrhosis because it offers a new way to support liver health by possibly reducing muscle wasting, which is a common issue for those with this condition. Unlike standard treatments that mainly focus on managing symptoms and complications, HMB may help by providing a nutrient that supports muscle mass and function. Additionally, the combination with a balanced amino acid mixture could enhance the body's ability to repair and regenerate tissues, offering a potential new avenue for improving patient outcomes.

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

This trial will compare the effects of Hydroxy Methyl Butyrate (HMB) and a Balanced Amino Acid Mixture on individuals with liver cirrhosis. Research has shown that HMB can help people with liver cirrhosis build muscle and improve physical abilities. One study found that patients who took HMB gained more muscle and performed better in physical tasks, suggesting it might help prevent muscle loss in people with cirrhosis.

Similarly, balanced amino acids, especially branched-chain amino acids (BCAAs), improve nutrition and reduce health problems in people with liver cirrhosis. Studies have found that BCAAs help manage protein use in the body and improve overall health in these patients. Both HMB and BCAAs show promise in addressing muscle issues related to cirrhosis, and this trial will evaluate their effectiveness. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with a moderate level of liver cirrhosis, as indicated by a Child-Pugh score of 5-8. Participants must not have had recent severe complications like gastrointestinal bleeding or infections, and should not be on dialysis or have uncontrolled diabetes among other exclusions.

Inclusion Criteria

I have been diagnosed with cirrhosis of the liver.

My liver function is moderately impaired.

Exclusion Criteria

My cancer has spread to other parts of my body.

I have been diagnosed with severe brain function problems.

I am on dialysis for kidney failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Acute Treatment

Participants receive acute administration of hydroxymethyl butyrate (HMB) enriched essential amino acids

1 day

1 visit (in-person)

Long-term Treatment

Participants receive long-term administration of hydroxymethyl butyrate (HMB) enriched essential amino acids for 3 months

12 weeks

Multiple visits (in-person) for muscle biopsies and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Balanced Amino Acids
• Hydroxy Methyl Butyrate

Trial Overview The study is testing whether HMB enriched amino acids can reverse muscle loss in people with cirrhosis. It compares this intervention to a balanced amino acid mixture that doesn't stimulate protein synthesis, over an acute phase and then long-term for three months.

How Is the Trial Designed?

Group I: Balanced Amino Acid Mixture Experimental Treatment 1 Intervention

Group II: Hydroxy Methyl Butyrate 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

In a study of 43 malnourished cirrhotic patients, oral nutritional supplements enriched with ß-Hydroxy-ß-methylbutyrate (HMB) significantly increased plasma levels of branched chain amino acids (BCAA) compared to a high-protein control, suggesting a potential therapeutic benefit in managing hepatic encephalopathy.

The HMB-enriched supplements improved the amino acid profile without raising harmful levels of ammonia, indicating a safe approach to potentially prevent minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino Acid Profile in Malnourished Patients with Liver Cirrhosis and Its Modification with Oral Nutritional Supplements: Implications on Minimal Hepatic Encephalopathy. Espina, S., Gonzalez-Irazabal, Y., Sanz-Paris, A., et al.[2021]

In a study involving Wistar rats with induced cholestasis, butyrate treatment significantly reduced harmful inflammatory cytokines and increased protective IL-10 levels, suggesting its potential to improve intestinal inflammation in cirrhosis.

Butyrate also enhanced the expression of tight junction proteins in the ileum and promoted the growth of beneficial gut bacteria, indicating its role in maintaining gut barrier integrity and microbiota diversity in liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Butyrate administration strengthens the intestinal epithelium and improves intestinal dysbiosis in a cholestasis fibrosis model. Peña-Rodríguez, M., Vega-Magaña, N., García-Benavides, L., et al.[2021]

In a study of 5618 patients with cirrhosis followed for a median of 3 years, nearly 60% of patients were prescribed potentially unsafe drugs, highlighting a significant risk for adverse drug reactions (ADRs).

The most commonly used medications included proton pump inhibitors and diuretics, with almost half of all prescriptions falling under safety recommendations, indicating a need for personalized pharmacotherapy to enhance safety in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Drug Prescriptions and Potential Safety in Patients with Cirrhosis: A Retrospective Real-World Study. Weersink, RA., Taxis, K., Drenth, JPH., et al.[2020]

In a study of 400 patients with liver cirrhosis, 20% of prescribed drugs were inadequately dosed, leading to a significant number of adverse drug reactions (ADRs), with 78% of these being preventable.

Patients receiving inadequately dosed medications experienced more ADRs and were more likely to be hospitalized, resulting in an additional 94 hospital days, highlighting the critical need for careful drug dosing in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose adjustment in patients with liver cirrhosis: impact on adverse drug reactions and hospitalizations. Franz, CC., Hildbrand, C., Born, C., et al.[2021]

BCAA supplementation in liver cirrhosis has been shown to slightly increase muscle mass and improve symptoms of hepatic encephalopathy, making it a useful second-line therapy.

While HMB supplementation may help increase muscle mass in chronic diseases, its effectiveness in liver cirrhosis is not well established, and it currently has no clinical indication for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Branched-Chain Amino Acids and Their Derivative β-Hydroxy-β-Methylbutyrate in Liver Cirrhosis. Espina, S., Sanz-Paris, A., Bernal-Monterde, V., et al.[2022]

In a pilot study involving 24 patients with liver cirrhosis, 12 weeks of beta-hydroxy-beta-methylbutyrate (HMB) supplementation significantly improved muscle function and increased quadriceps muscle mass compared to a placebo.

HMB supplementation was well tolerated with no reported adverse events, and it also led to a reduction in the Liver Frailty Index, indicating potential benefits for frailty in cirrhotic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of 12-Week Beta-Hydroxy-Beta-Methylbutyrate Supplementation in Patients with Liver Cirrhosis: Results from a Randomized Controlled Single-Blind Pilot Study. Lattanzi, B., Bruni, A., Di Cola, S., et al.[2021]

In a study of 43 patients with liver cirrhosis and malnutrition, those receiving HMB supplementation showed trends towards improved handgrip strength and reduced minimal hepatic encephalopathy over 12 weeks, although fat-free mass did not change.

Both HMB and non-HMB supplements led to increased fat mass and improved liver function scores, indicating that while HMB may have specific benefits, overall nutritional support is crucial for patients with cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Clinical Trial: Effects of β-Hydroxy-β-Methylbutyrate (HMB)-Enriched vs. HMB-Free Oral Nutritional Supplementation in Malnourished Cirrhotic Patients. Espina, S., Sanz-Paris, A., Gonzalez-Irazabal, Y., et al.[2022]

Patients with cirrhosis experience unpredictable changes in how their bodies process medications, leading to potential drug accumulation and adverse effects, especially for drugs primarily cleared by the liver.

Certain medications, like aminoglycosides and ACE inhibitors, should be avoided in patients with cirrhosis due to increased risks of toxicity and complications, while drugs like furosemide may cause electrolyte disturbances without significantly altering their disposition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug administration in chronic liver disease. Westphal, JF., Brogard, JM.[2022]

Medicine-related problems (MRPs) are common in patients with liver cirrhosis, with reported frequencies ranging from 14% to 23.4% across various studies, highlighting a significant concern in this patient population.

The causes of MRPs include drug interactions, inappropriate dosing, and the use of contraindicated medications, along with patient-related factors and healthcare system issues, indicating that effective management should address both medication therapy and patient behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medicine use and medicine-related problems in patients with liver cirrhosis: a systematic review of quantitative and qualitative studies. Cheema, E., Al-Aryan, A., Al-Hamid, A.[2020]

In healthy rats, HMB supplementation improved muscle mitochondrial function and increased levels of branched-chain amino acids (BCAAs) in the blood, although it did not significantly affect muscle mass or protein content.

In rats with liver cirrhosis induced by carbon tetrachloride, HMB supplementation led to negative outcomes, including higher mortality and lower body weight, suggesting that HMB may have harmful effects in the context of liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of beta-hydroxy-beta-methylbutyrate supplementation on skeletal muscle in healthy and cirrhotic rats. Holeček, M., Vodeničarovová, M.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9631141/

Branched-chain amino acids supplementation has ... The conclusion is that branched-chain amino acids reduce the incidence of complications in patients with liver cirrhosis and ameliorate nutritional status.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9220261/

The Emerging Role of Branched-Chain Amino Acids ... However, BCAA supplementation was found to provide positive outcomes in cirrhosis and HCC patients. This review will attempt to address the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0022316622102919

Branched-Chain Amino Acid Supplementation in Patients ... Several studies have shown that BCAA supplementation is effective in downregulating protein metabolism in cirrhosis, improving nitrogen balance, and finally ...

4. eymj.org eymj.org/DOIx.php?id=10.3349/ymj.2024.0436

Oral Branched-Chain Amino Acids as a Cost-Effective ... Oral BCAA treatment prevented 34% of HE recurrences and reduced the number of HE-related deaths by 18%. Although patients in the BCAA-treated ...

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New Evidence of Oral Branched-Chain Amino Acid... Patients with liver cirrhosis have decreased serum concentrations of BCAAs; a group of 3 essential amino acids comprising valine, leucine, and isoleucine; and a ...

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Branched chain amino acids in hepatic encephalopathy ... The aim of this review is to analyze scientific evidence supporting the administration of BCAAs in patients with liver cirrhosis affected by HE and sarcopenia.

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Side Effects of Amino Acid Supplements - PMC The aim of the article is to examine side effects of increased dietary intake of amino acids, which are commonly used as a dietary supplement.

8. journals.lww.com journals.lww.com/md-journal/fulltext/2017/06160/effects_of_branched_chain_amino_acids__bcaas__on.1.aspx

Effects of branched-chain amino acids (BCAAs) on the... Long-term oral BCAA supplementation has beneficial effects in patients with advanced liver cirrhosis. A further large-scale prospective study is needed to ...

9. nature.com nature.com/articles/s41392-023-01569-3

Amino acid metabolism in health and disease Amino acid metabolism disorders have been linked with a number of pathological conditions, including metabolic diseases, cardiovascular diseases, immune ...