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

Trial Summary

What is the purpose of this trial?

This trial involves patients taking a special treatment called HA35 for several months. The goal is to see if HA35 improves health markers like muscle strength and body composition. Participants will undergo various tests to measure these effects.

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.

What data supports the idea that Sodium Hyaluronate for Alcoholic Hepatitis is an effective treatment?

The available research does not provide any data supporting the effectiveness of Sodium Hyaluronate for treating Alcoholic Hepatitis. The studies mentioned focus on its use for other conditions, such as sinus issues, corneal defects, and dry eye syndrome, showing improvements in those areas. However, there is no information on its effectiveness for Alcoholic Hepatitis compared to other treatments. ^{1 2 3 4 5}

What safety data exists for Sodium Hyaluronate in treating alcoholic hepatitis?

The provided research does not contain specific safety data for Sodium Hyaluronate in the treatment of alcoholic hepatitis. The studies focus on other treatments and emerging therapies for alcoholic liver disease and alcoholic hepatitis, but Sodium Hyaluronate is not mentioned. ^{6 7 8 9 10}

Is Sodium Hyaluronate a promising drug for treating Alcoholic Hepatitis?

Sodium Hyaluronate shows promise as a drug for treating Alcoholic Hepatitis because it can help measure liver damage without needing a liver biopsy, which is a more invasive procedure. It also has the potential to reverse liver damage caused by alcohol if the person stops drinking. ^{11 12 13 14 15}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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Hyaluronan plus saline nasal washes in the treatment of rhino-sinusal symptoms in patients undergoing functional endoscopic sinus surgery for rhino-sinusal remodeling. [2017]

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Effects of Topical 1% Sodium Hyaluronate and Hydroxypropyl Methylcellulose in Treatment of Corneal Epithelial Defects. [2020]

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Endoscopic and clinical benefits of hyaluronic acid in children with chronic adenoiditis and middle ear disease. [2018]

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Double-blind, randomised controlled trial on the efficacy of saline nasal irrigation with sodium hyaluronate after endoscopic sinus surgery. [2019]

5. England 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. [2019]

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Treatment of alcoholic liver disease. [2013]

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[Effect of domestic glutathione on the alcoholic liver disease]. [2013]

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Emerging medical therapies for non-alcoholic fatty liver disease and for alcoholic hepatitis. [2023]

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Current concepts and controversies in the treatment of alcoholic hepatitis. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Characteristics of serum hyaluronate concentrations in patients with alcoholic liver disease. [2004]

12. England pubmed.ncbi.nlm.nih.gov

Histochemical study of hyaluronate in alcoholic liver disease. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Serum hyaluronate correlates with histological progression in alcoholic liver disease. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Assessment of prognosis in alcoholic liver disease: can serum hyaluronate replace liver biopsy? [2019]

15. United States pubmed.ncbi.nlm.nih.gov

Hyaluronan synthesis inhibition normalizes ethanol-enhanced hepatic stellate cell activation. [2023]