Sodium Hyaluronate for Non-Alcoholic Fatty Liver Disease

Overseen By Annette Bellar

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: The Cleveland Clinic

Must not be taking: Corticosteroids, Tamoxifen, Estrogen, others

Disqualifiers: Cancer, Diabetes, Hypertension, Liver disease, others

Compensation: Varies

Number of Visits: 4

Duration: 3 days

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether sodium hyaluronate can help individuals with non-alcoholic fatty liver disease, a condition where fat accumulates in the liver. Participants will take a capsule, which may contain the treatment or a placebo, for three days. The study includes a day of medical exams and tests to assess the treatment's effects on the body. It suits those who consume fewer than 7 drinks per week for women and 14 for men and do not have chronic illnesses like uncontrolled diabetes or heart disease. Participants should be prepared for medical appointments and arrange for a driver to take them home after the study visit. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

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

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that alter muscle protein synthesis, like certain steroids or hormone treatments.

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

Research has shown that sodium hyaluronate is a substance naturally found in the body, including in the liver. Although specific information about its safety for treating non-alcoholic fatty liver disease (NAFLD) is limited, it is generally considered safe. It is commonly used in medical treatments like eye surgeries and for relieving joint pain, with a good safety record in those areas.

This trial is in the early stages, focusing on the safety of sodium hyaluronate for humans, particularly for liver conditions like NAFLD. As an early phase trial, sodium hyaluronate is expected to be safe based on its other uses, but researchers are still gathering specific safety information related to liver disease. Study participants will be closely monitored for any side effects or reactions to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver disease?

Sodium Hyaluronate is unique because it offers a new approach to treating Non-Alcoholic Fatty Liver Disease (NAFLD). Unlike the standard treatments that often focus on lifestyle changes and managing symptoms with medications like vitamin E or pioglitazone, Sodium Hyaluronate introduces a novel active ingredient. This compound is known for its anti-inflammatory properties and ability to support tissue health, potentially addressing liver inflammation and damage directly. Researchers are excited because this treatment could offer a more targeted and efficient way to improve liver health, showing promise in just a few days compared to the longer timelines of existing therapies.

What evidence suggests that Sodium Hyaluronate might be an effective treatment for Non-Alcoholic Fatty Liver Disease?

Research has shown that sodium hyaluronate, also known as hyaluronic acid, might help treat liver issues such as non-alcoholic fatty liver disease (NAFLD). Some studies have highlighted hyaluronic acid as an indicator of liver health, particularly in serious liver diseases. It may reduce liver inflammation and scarring. Although more research is needed specifically for NAFLD, early studies suggest it could help manage liver problems. In this trial, participants will receive either sodium hyaluronate or a placebo to evaluate its potential to improve liver health, potentially benefiting those with NAFLD. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for healthy individuals who drink alcohol moderately (up to 7 drinks per week for women and up to 14 for men). They must understand the study and consent in writing. People with uncontrolled diabetes, thyroid issues, hypertension, liver disease, heart problems, kidney failure, pregnancy, abnormal blood clotting or on certain medications like steroids or hormones cannot participate.

Inclusion Criteria

Ability to understand and willingness to provide written consent

I drink less than 7 (if woman) or 14 (if man) alcoholic drinks per week.

Exclusion Criteria

You have had a problem with drinking alcohol in the past.

I have a liver condition.

My blood pressure or cholesterol levels are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Baseline

Collection of blood, urine, and stool samples, body composition measurements, and randomization into HA35 or placebo groups

1 day

1 visit (in-person)

Treatment

Participants take HA35 or placebo capsule daily for 3 days

3 days

Study Visit

Participants undergo a medical exam, clinical labs, questionnaires, body composition measurements, and urine and stool collections. They also consume a sugar cocktail to measure gut permeability, participate in an acute ethanol challenge, and undergo two muscle biopsies.

1 day

1 visit (in-person)

Follow-up

Participants return to drop off the 24-hour urine collection

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sodium Hyaluronate

Trial Overview The trial tests Sodium Hyaluronate's effects compared to a placebo over three days followed by assessments including medical exams and muscle biopsies after an acute ethanol challenge. Participants will also measure gut permeability using a sugar cocktail.

How Is the Trial Designed?

Group I: HA35 Treatment Group Active Control 1 Intervention

12 study participants will be given an HA35 capsule to take once per day in the morning with breakfast for 3 days.

Group II: HA35 Placebo Group Placebo Group 1 Intervention

12 study participants will be given a placebo capsule to take once per day in the morning with breakfast for 3 days.

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 levels of hyaluronic acid (HA), TNF-alpha, and IL-8 were significantly elevated in patients with nonalcoholic steatohepatitis (NASH) compared to healthy controls, indicating a potential inflammatory response associated with the disease.

While HA levels were higher in patients with cirrhosis than in those with NASH, the study found no significant correlation between these serum markers and the severity of liver histopathology, suggesting that while they may indicate liver damage, they are not reliable indicators of disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis. Bahcecioglu, IH., Yalniz, M., Ataseven, H., et al.[2022]

In a study of 52 patients with nonalcoholic fatty liver disease (NAFLD), serum levels of hyaluronic acid (HA) did not show significant differences across varying degrees of liver steatosis or steatohepatitis, suggesting it may not be a reliable marker for diagnosing these conditions.

The study found a significant correlation between steatosis levels measured by CT and biopsy results, indicating that while HA levels were not useful, imaging techniques may still play a role in assessing liver health in NAFLD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of serum hyaluronic acid in predicting necroinflammatory activity of the nonalcoholic fatty liver disease. Guveli, H., Ovunc Kurdas, O.[2022]

In a study of 106 overweight or obese Caucasian children with biopsy-proven non-alcoholic fatty liver disease (NAFLD), higher plasma levels of hyaluronic acid (HA) and N-terminal propeptide of type III procollagen (PIIINP) were significantly associated with more advanced liver fibrosis stages (F2 compared to F0 or F1).

The study found that elevated levels of HA and PIIINP were linked to lower estimated glomerular filtration rate (eGFR) values, indicating potential kidney function impairment, independent of the PNPLA3 rs738409 genotype and other factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Levels of Plasma Hyaluronic Acid and N-terminal Propeptide of Type III Procollagen Are Associated With Lower Kidney Function in Children With Non-alcoholic Fatty Liver Disease. Mosca, A., Mantovani, A., Crudele, A., et al.[2022]

In a study of 79 patients with non-alcoholic fatty liver disease (NAFLD), serum hyaluronic acid levels were found to significantly correlate with the severity of liver fibrosis, indicating its potential as a reliable biomarker.

A serum hyaluronic acid cut-off value of 46.1 µg/L showed high sensitivity (85%) and specificity (80%) for identifying severe fibrosis, making it a useful tool for clinicians in assessing liver health in NAFLD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyaluronic acid, an accurate serum marker for severe hepatic fibrosis in patients with non-alcoholic fatty liver disease. Suzuki, A., Angulo, P., Lymp, J., et al.[2015]

Non-alcoholic fatty liver disease (NAFLD) is a widespread liver condition linked to obesity, characterized by fat accumulation in the liver, and currently has limited treatment options beyond diet and exercise.

Recent studies, including randomized controlled trials and animal models, suggest that certain natural products, like spirulina, garlic, and resveratrol, may effectively alleviate NAFLD symptoms, highlighting their potential as alternative therapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them? Tarantino, G., Balsano, C., Santini, SJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5063891/

Hyaluronic acid concentration in liver diseases These include alcoholic and non-alcoholic steatohepatitis, hepatitis B, C and others [5, 6]. In these clinical conditions HA might be used ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9243755/

Role of serum hyaluronic acid in predicting ... Globally, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is defined by the presence of 5% hepatic steatosis (HS) in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1550413124000901

New and emerging treatments for metabolic dysfunction- ... A disease-specific quality of life instrument for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: CLDQ-NAFLD. Liver Int.

4. scholars.duke.edu scholars.duke.edu/publication/1377447

Hyaluronic acid, an accurate serum marker for severe hepatic ... Hyaluronic acid, an accurate serum marker for severe hepatic fibrosis in patients with non-alcoholic fatty liver disease. Liver Int. 2005 Aug;25(4):779–86.

5. researchgate.net researchgate.net/publication/281683584_Hyaluronic_acid_concentration_in_liver_diseases

(PDF) Hyaluronic acid concentration in liver diseases Methods: We tested serum specimens from 57 patients with alcoholic cirrhosis, 30 with nonalcoholic cirrhosis, and 22 with toxic hepatitis (TH).

6. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024044992

A comprehensive updated review of risk factors, symptoms ... Non-alcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease and a progressive and chronic liver disorder with a ...

7. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.615978/full

Liver Fibrosis in Non-alcoholic Fatty Liver Disease The abnormal amount of liver fat triggers inflammation by infiltrating immune cells and secretion of cytokines. This is called non-alcoholic steatohepatitis or ...

8. link.springer.com link.springer.com/article/10.1007/s00535-021-01796-x

Evidence-based clinical practice guidelines for ... Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults.