Sodium Hyaluronate for Alcoholic Hepatitis

Overseen By Annette Bellar

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: The Cleveland Clinic

Must not be taking: Anticoagulants, Muscle metabolism drugs

Disqualifiers: Pregnancy, Renal failure, Malignancy, others

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for alcoholic hepatitis, a liver condition caused by heavy alcohol use. Researchers are testing whether sodium hyaluronate, a compound often used for its potential therapeutic effects, can improve liver health and overall well-being in affected individuals. Participants will take a daily capsule for 90 days and attend two study visits for tests and assessments. Ideal participants are those diagnosed with alcoholic hepatitis who have been heavy drinkers for at least six months. As an Early Phase 1 trial, this study focuses on understanding how this new treatment works in people, offering participants a chance to be among the first to receive it.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on medications that alter muscle protein metabolism or use anti-platelet/anticoagulation drugs or medications that interfere with blood clotting.

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

Research has shown that sodium hyaluronate (HA35), currently under testing for alcoholic hepatitis, appears safe. In studies, patients have generally tolerated HA35 well, with no reports of serious side effects directly linked to the treatment. Sodium hyaluronate is a purified form of hyaluronic acid, already used in other medical treatments, indicating its general safety. However, this trial remains in the early stages. While initial results are promising, more information is needed to fully understand its safety for this specific condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholic hepatitis?

Researchers are excited about using sodium hyaluronate (HA35) for alcoholic hepatitis because it introduces a new approach by potentially reducing liver inflammation and promoting healing. Unlike standard treatments that mainly focus on managing symptoms with steroids and nutritional therapy, HA35 uses its unique property as a component of connective tissues to support liver function directly. This novel mechanism might offer a more targeted and effective way to treat alcoholic hepatitis, providing hope for improved outcomes in patients suffering from this condition.

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

Research suggests that sodium hyaluronate, particularly a type called HA35, might aid in treating alcoholic hepatitis. In animal studies, HA35 improved liver damage and reduced alcohol-induced inflammation by balancing a part of the body's response to alcohol. These early results are promising, but they are based on animal studies. This trial will compare the effects of HA35 with a placebo in participants receiving standard care for alcoholic hepatitis. More research is needed to determine if these benefits apply to humans. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults who've been drinking heavily (over 60g/day for men, over 40g/day for women) and have moderate alcoholic hepatitis but not severe liver damage or other serious health issues. Pregnant women, those with recent surgeries, kidney failure, certain blood disorders, active infections or cancers can't participate.

Inclusion Criteria

I have been diagnosed with alcoholic hepatitis, meet the alcohol intake criteria, and my liver function tests match the specified levels.

Exclusion Criteria

I am unable to give consent myself.

I have liver disease not only from alcohol.

Creatinine >2mg/dL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive either HA35 or placebo for 90 days with assessments at the start and end of the period

12 weeks

2 visits (in-person), 2 visits (phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Not Applicable

Trial Overview Participants will take either Sodium Hyaluronate or a placebo capsule daily for 90 days to see if it helps with alcoholic hepatitis. They'll have two in-person visits with exams and tests plus phone check-ins. A muscle biopsy and gut permeability test are also part of the study.

How Is the Trial Designed?

Group I: HA35 Treatment Group Active Control 1 Intervention

24 study participants will receive the standard of care treatment for AH and a 90-day supply of a HA35 to take once a day with breakfast.

Group II: HA35 Placebo Group Placebo Group 1 Intervention

24 study participants will receive the standard of care treatment for AH and a 90-day supply of a placebo to take once a day with breakfast.

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

Serum hyaluronate (HA) concentrations are significantly elevated in patients with alcoholic liver disease (ALD) compared to those with non-ALD, particularly in individuals actively drinking, indicating a potential biomarker for liver damage.

In patients with ALD, serum HA levels decrease to non-ALD levels after 4 weeks of abstinence from alcohol, suggesting that alcohol consumption directly influences HA concentrations and may be linked to the progression of hepatic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of serum hyaluronate concentrations in patients with alcoholic liver disease. Tsutsumi, M., Urashima, S., Takase, S., et al.[2004]

Currently, the main treatment for alcoholic liver disease involves abstaining from alcohol and ensuring proper nutrition, with corticosteroids being the only specific therapy shown to improve survival in severe cases.

Potential new therapies include dietary supplements like polyunsaturated lecithin, which may prevent liver damage, and various approaches targeting cytokines and collagen synthesis to reduce liver injury and promote healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of alcoholic liver disease. Mezey, E.[2013]

In a pilot study involving 46 patients who underwent functional endoscopic sinus surgery, nebulized sodium hyaluronate (9 mg) significantly improved nasal dyspnoea, ciliary motility, and the appearance of nasal mucosa compared to saline alone.

The treatment was well tolerated and showed a high probability of success in alleviating symptoms, with the most notable improvement seen in nasal dyspnoea, indicating its potential effectiveness in enhancing recovery after sinus surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyaluronan plus saline nasal washes in the treatment of rhino-sinusal symptoms in patients undergoing functional endoscopic sinus surgery for rhino-sinusal remodeling. Macchi, A., Terranova, P., Digilio, E., et al.[2017]

In a study involving 13 patients with alcoholic liver disease (ALD) and 10 with non-ALD, it was found that alcohol consumption significantly increases hyaluronic acid (HA) levels in the liver, which is associated with liver damage.

The study also showed that abstaining from alcohol led to a decrease in HA levels in the liver, suggesting that the increase in HA deposition due to alcohol is reversible with abstinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histochemical study of hyaluronate in alcoholic liver disease. Urashima, S., Tsutsumi, M., Shimanaka, K., et al.[2019]

Chronic ethanol consumption increases the activation of hepatic stellate cells (HSCs) through enhanced production of hyaluronan (HA), which contributes to liver injury and fibrosis in alcohol-associated liver disease (ALD).

Inhibiting HA synthesis with 4-methylumbelliferone (4MU) effectively normalized HSC activation and reduced liver injury markers, suggesting that targeting HA production could be a potential therapeutic strategy for managing ALD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyaluronan synthesis inhibition normalizes ethanol-enhanced hepatic stellate cell activation. Kotulkar, M., Robarts, DR., Lin-Rahardja, K., et al.[2023]

In a study of 103 children with chronic adenoiditis, daily topical administration of hyaluronic acid (HA) significantly reduced the number of acute otitis media episodes, indicating its efficacy in managing this condition.

The treatment was found to be safe, with no adverse effects reported, and it improved endoscopic outcomes better than saline solution alone, highlighting its potential as a beneficial therapy for children with recurrent ear infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic and clinical benefits of hyaluronic acid in children with chronic adenoiditis and middle ear disease. Torretta, S., Marchisio, P., Rinaldi, V., et al.[2018]

In a study involving 56 patients who underwent functional endoscopic sinus surgery, the addition of sodium hyaluronate to nasal saline irrigation significantly improved both endoscopic appearance and patient satisfaction compared to saline alone.

The results suggest that sodium hyaluronate could be an effective adjunct treatment in the early post-operative care for patients recovering from chronic rhinosinusitis surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomised controlled trial on the efficacy of saline nasal irrigation with sodium hyaluronate after endoscopic sinus surgery. Mozzanica, F., Preti, A., Gera, R., et al.[2019]

In a randomized, double-blind crossover trial involving 70 subjects, a 0.1% hyaluronan solution significantly improved objective measures of dry eye syndrome, such as Schirmer's score and rose bengal staining score, compared to 0.9% saline.

Subjects reported that hyaluronan was more effective than saline in relieving symptoms like burning and grittiness, and no adverse events were linked to hyaluronan treatment, indicating it is safe and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double blind, randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1% (w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome. Condon, PI., McEwen, CG., Wright, M., et al.[2019]

Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most prevalent liver diseases globally, with alcoholic hepatitis (AH) presenting a particularly high risk of short-term mortality.

Currently, there are no FDA-approved treatments for NAFLD or ALD, but recent years have seen significant advancements in research, with many new therapeutic agents being tested in clinical trials for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging medical therapies for non-alcoholic fatty liver disease and for alcoholic hepatitis. Wong, VW., Singal, AK.[2023]

Only 15-20% of chronic alcohol misusers develop cirrhosis, but it is currently impossible to predict who will progress to severe liver disease, highlighting the need for better diagnostic tools.

Serum hyaluronic acid is a promising non-invasive test that may help estimate fibrosis severity in alcoholic liver disease, potentially reducing the need for risky liver biopsies, although it is not yet a replacement for biopsy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of prognosis in alcoholic liver disease: can serum hyaluronate replace liver biopsy? Phillips, MG., Preedy, VR., Hughes, RD.[2019]

In a study involving 30 rabbits with alkali-induced corneal defects, treatment with 1% sodium hyaluronate significantly accelerated the healing process compared to both saline and hydroxypropyl methylcellulose (HPMC).

Sodium hyaluronate was found to be an effective wound-healing adjuvant for corneal epithelial defects, outperforming HPMC in promoting faster recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Topical 1% Sodium Hyaluronate and Hydroxypropyl Methylcellulose in Treatment of Corneal Epithelial Defects. Shahraki, K., Hosseini, SR., Amini Fard, A., et al.[2020]

Light to moderate daily alcohol consumption may protect against non-alcoholic fatty liver disease (NAFLD), but it poses risks for other conditions like breast and colon cancer.

Individuals with underlying liver conditions such as non-alcoholic steatohepatitis (NASH) should completely avoid alcohol, as even moderate consumption can worsen liver health and increase the risk of hepatocellular cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of chronic alcohol consumption on the development and progression of non-alcoholic fatty liver disease (NAFLD). Seitz, HK., Mueller, S., Hellerbrand, C., et al.[2020]

In a study involving 110 patients with alcoholic liver disease, both domestic glutathione (GSH) and TAD treatments showed similar improvements in liver function markers (ALT, AST) after 30 days, indicating comparable efficacy.

GSH was well-tolerated and safe, suggesting it can be a viable option for improving clinical signs and liver function in patients with alcoholic liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of domestic glutathione on the alcoholic liver disease]. Zhang, Q., Guo, S., Hu, D., et al.[2013]

In a study of 87 patients with various stages of alcoholic liver disease, serum hyaluronate levels significantly increased with the severity of liver damage, indicating its potential as a reliable marker for detecting early stages of liver disease.

Hyaluronate levels correlated well with liver histology, making it a sensitive predictor for the presence of moderate hepatic fibrosis, which could help in monitoring liver health in individuals with chronic alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum hyaluronate correlates with histological progression in alcoholic liver disease. Stickel, F., Poeschl, G., Schuppan, D., et al.[2019]

Glucocorticoids are the primary treatment for severe alcoholic hepatitis, highlighting their established efficacy in managing this condition.

The review discusses the evolution of scoring systems, including the Glasgow alcoholic hepatitis score, and evaluates various treatment interventions, indicating ongoing research and debate in the field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current concepts and controversies in the treatment of alcoholic hepatitis. Rongey, C., Kaplowitz, N.[2019]

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A small specific-sized hyaluronic acid ameliorates ... Furthermore, oral supplementation with HA35 ameliorated ethanol-induced liver injury and inflammation in mice. These findings suggest that HA35 ...

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Hyaluronic acid 35 normalizes TLR4 signaling in Kupffer ... Treatment of hepatic macrophages after chronic ethanol feeding with small-specific sized hyaluronic acid 35 (HA35) normalizes TLR4 signaling.

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HA35 Moderate Alcoholic Hepatitis (AH) Study Clinical diagnosis of alcoholic hepatitis defined as: Regular consumption of alcohol with an intake of >60 g daily or >420 g weekly onaverage ...

8. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf8/p080020b.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) derivative of highly purified sodium hyaluronate (hyaluronan) extracted from chicken combs. ... alcohol abuse that, in the opinion of the ...