HMB-Enriched Supplement for Alcoholic Liver Disease and COVID-19

Overseen By Alina Tuladhar, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Must not be taking: Anticoagulants, Antiplatelets, Muscle metabolism

Disqualifiers: Ventilator support, Pregnancy, Advanced organ diseases, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a supplement called β-hydroxy β-methyl butyrate (HMB) to determine its potential benefits for people with COVID-19 who also have alcohol-related liver disease. Researchers aim to discover if HMB can prevent breathing problems and enhance recovery in these patients. Participants will receive either the HMB supplement or a regular amino acid supplement for 90 days. Suitable candidates include those with COVID-19 and lung issues, regardless of whether they have alcohol-related liver problems. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could improve future treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on anticoagulant therapy and medications that alter muscle protein metabolism, except for systemic corticosteroids. It's best to discuss your specific medications with the trial team.

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

Research has shown that HMB is generally safe for use. Studies have found that HMB can increase muscle mass and function without causing major side effects. One study linked HMB intake to lower cholesterol levels, which benefits health. HMB has also been used in other situations to prevent muscle breakdown and support muscle growth. No strong evidence of serious side effects exists with HMB, making it a promising option for those considering this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the HMB-enriched amino acid treatment because it introduces a new approach for tackling alcoholic liver disease and COVID-19. Unlike standard treatments that focus on managing symptoms or reducing inflammation, this treatment incorporates β-hydroxy β-methyl butyrate (HMB), which is thought to help in muscle preservation and improving liver health by reducing muscle breakdown and promoting protein synthesis. This unique mechanism of action offers a potential dual benefit, especially important for patients with compromised liver function and those battling COVID-19, where muscle wasting is a concern. The treatment's innovative use of HMB distinguishes it from typical therapies and offers hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for COVID-19 and alcoholic liver disease?

Research has shown that HMB, a compound that helps build muscle, may also boost the immune system. This could benefit people with COVID-19 and liver disease. In this trial, participants will be randomized into different treatment arms. One arm will receive an HMB-enriched amino acid supplement, known for its tissue-building properties. Some studies have found that supplements with HMB can improve liver function and overall health. These findings suggest that HMB might aid recovery and lower the risk of severe illness in patients with COVID-19 and alcohol-related liver disease. ^{1 3 6 7 8}

Who Is on the Research Team?

Srinivasan Dasarathy, MD

Principal Investigator

Staff

Are You a Good Fit for This Trial?

This trial is for adults over 21 with alcoholic liver disease (ALD) and COVID-19 pneumonia, who have a moderate level of liver impairment but not severe kidney issues or advanced organ diseases. They shouldn't be on certain muscle-affecting meds or blood thinners if in the biopsy group, need ventilator support, be pregnant, or have had recent gastrointestinal bleeding.

Inclusion Criteria

I have ALD and COVID-19 pneumonia with moderate liver disease.

I am over 21 and do not have alcoholic liver disease but have COVID-19 pneumonia.

I am over 21 and have ALD with COVID-19 pneumonia.

Exclusion Criteria

I am not on medication that changes muscle protein, except for corticosteroids.

I am currently taking blood thinners.

You need help breathing with a ventilator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either HMB enriched amino acid or balanced amino acid supplementation for 90 days

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Balanced amino acid
• β-hydroxy β-methyl butyrate (HMB) enriched amino acid

Trial Overview The study tests whether an HMB-enriched amino acid supplement can help prevent severe illness and improve recovery in patients with ALD affected by COVID-19. It looks at how this condition progresses naturally and if HMB affects breathing problems and overall health outcomes.

How Is the Trial Designed?

Group I: HMB enriched amino acid arm Active Control 1 Intervention

The patients randomized to the HMB enriched amino acid (HMB/EAA) arm will be given HMB/EAA for 90 days.

Group II: Balanced amino acid arm Placebo Group 1 Intervention

The patients randomized to the Balanced amino acid (BAA) arm will be given BAA for 90 days.

β-hydroxy β-methyl butyrate (HMB) enriched amino acid is already approved in United States, European Union for the following indications:

Approved in United States as β-hydroxy β-methyl butyrate for:

• Nutritional supplement for malnourished cirrhotic patients
• Muscle wasting prevention

Approved in European Union as HMB for:

• Nutritional support for liver cirrhosis patients
• Prevention of muscle wasting

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 46 individuals with alcohol use disorder and moderate alcohol-associated hepatitis, daily oral Lactobacillus rhamnosus GG (LGG) significantly reduced liver injury after just one month of treatment.

After six months of LGG treatment, participants showed a marked decrease in heavy drinking, reaching levels of social drinking or abstinence, indicating potential benefits for both liver health and alcohol consumption behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Beneficial Effects of Lactobacillus GG Therapy on Liver and Drinking Assessments in Patients with Moderate Alcohol-Associated Hepatitis. Vatsalya, V., Feng, W., Kong, M., et al.[2023]

In a pilot study involving 25 participants with mild to moderate alcohol use disorder, a high dose of essential amino acid supplement (EAAS) significantly reduced intrahepatic lipid (IHL) by 23% after 4 weeks, indicating potential benefits for liver health.

The low dose of EAAS did not show significant changes in IHL, suggesting that higher dosages may be necessary for efficacy in reducing liver fat in individuals with alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Essential Amino Acid Supplement Lowers Intrahepatic Lipid despite Excess Alcohol Consumption. Coker, MS., Ladd, KR., Kim, J., et al.[2022]

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]

Sodium butyrate (NaB) effectively improved non-alcoholic fatty liver disease (NAFLD) in mice by restoring gut microbiota balance and increasing beneficial bacteria, which helped reduce liver inflammation and fat accumulation.

After 8 weeks of NaB treatment, significant improvements were observed in liver function and metabolic indices, indicating its potential as a therapeutic agent for NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier. Zhou, D., Pan, Q., Xin, FZ., 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 on mice, gut microbiota-derived propionate showed protective effects against alcohol-related liver disease (ALD) by improving gut-liver axis homeostasis and intestinal permeability.

Propionate supplementation not only prevented liver damage and fat accumulation but also reduced intestinal inflammation and restored gut barrier function, suggesting it could be a potential treatment for ALD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propionate Ameliorates Alcohol-Induced Liver Injury in Mice via the Gut-Liver Axis: Focus on the Improvement of Intestinal Permeability. Xu, Q., Zhang, R., Mu, Y., et al.[2022]

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 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]

In a study of 47 patients on the liver transplantation waiting list, both β-hydroxy β-methylbutyrate (HMB) and a control supplement improved muscle mass (measured by arm circumference) and strength (measured by dynamometry) over 12 weeks, indicating potential benefits of HMB supplementation.

Both groups showed a decrease in the frailty index, suggesting improved functionality and quality of life, although the specific advantages of HMB over the control were not clearly established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of β-hydroxy β-methylbutyrate (HMB) with nutritional counselling on anthropometric muscle mass markers, strength, functionality, and quality of life in patients on the waiting list for liver transplantation: A double-blind study. Ferreira, SC., Souza, NP., Amado, LRN., et al.[2023]

Fecal microbiota transplantation (FMT) shows promise as a treatment for severe alcoholic hepatitis (SAH), addressing the limitations of current steroid therapies, which only benefit a third of patients and have uncertain long-term effects.

Initial human trials indicate that FMT can improve disease severity and survival rates in SAH patients, suggesting it may become a new standard of care with fewer side effects compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in alcohol related liver diseases. Shasthry, SM.[2021]

Severe alcoholic hepatitis (AH), identified by a Maddrey score of ≥ 32, has a poor prognosis and is traditionally treated with a 28-day course of prednisone, which has shown to reduce short-term mortality but not improve long-term survival.

New therapeutic approaches, such as N-acetyl-cysteine combined with steroids, and potential future treatments targeting liver regeneration and gut microbiota modulation, are being explored in clinical trials to improve outcomes for patients with AH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of severe alcoholic hepatitis: past, present and future. Lanthier, N., Stärkel, P.[2018]

A study of 410 fecal samples from 212 Korean twins found that higher levels of the butyrate-producing bacteria Roseburia are linked to lower alcohol use disorder scores, suggesting a protective role against alcohol-related liver diseases (ALDs).

In murine models of ALD, administering Roseburia spp. improved liver conditions by enhancing gut barrier integrity and restoring gut microbiota, indicating that these bacteria could be a potential therapeutic target for preventing ALDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roseburia spp. Abundance Associates with Alcohol Consumption in Humans and Its Administration Ameliorates Alcoholic Fatty Liver in Mice. Seo, B., Jeon, K., Moon, S., et al.[2020]

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