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

Trial Summary

What is the purpose of this trial?

Eligible subjects will be asked to take a placebo/treatment capsule for a total of 3 days and then participate in a study visit on the fourth day. This study visit will include a medical exam, clinical labs, questionnaires, body composition measurements, and urine and stool collections. Additionally, participants will consume a sugar cocktail to measure their gut permeability, participate in an acute ethanol challenge, and undergo two muscle biopsies. The study will take approximately 3-4 hours and a designated driver will need to drive the participant home. On the fifth day, you will be asked to return to drop of the 24-hour urine collection.

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.

How is Sodium Hyaluronate different from other treatments for non-alcoholic fatty liver disease?

Sodium Hyaluronate (Hyaluronic Acid) is unique because it is being explored as a treatment option for non-alcoholic fatty liver disease (NAFLD) due to its role as a non-invasive marker for liver fibrosis, which is a key feature of NAFLD. Unlike other treatments that focus on lifestyle changes, Sodium Hyaluronate offers a potential therapeutic approach by targeting the extracellular matrix involved in liver fibrosis. ^{1 2 3 4 5}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

Role of serum hyaluronic acid in predicting necroinflammatory activity of the nonalcoholic fatty liver disease. [2022]

2. Switzerland 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. [2022]

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

Hyaluronic acid, an accurate serum marker for severe hepatic fibrosis in patients with non-alcoholic fatty liver disease. [2015]

4. Switzerland pubmed.ncbi.nlm.nih.gov

It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them? [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis. [2022]