Milk Thistle for Pediatric Fatty Liver Disease

Overseen By Alok Bapatla, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Thomas J Sferra, MD

Disqualifiers: Cardiovascular disorders, Malignancy, Transplantation, Immunologic diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Milk Thistle for Pediatric Fatty Liver Disease?

Research shows that silymarin, the active component of milk thistle, has antioxidant, anti-inflammatory, and antifibrotic properties, which have been beneficial in treating liver diseases like nonalcoholic fatty liver disease (NAFLD) in adults. Some studies have demonstrated that silymarin can improve liver conditions by reducing liver fat, inflammation, and damage. ^{1 2 3 4 5}

Is milk thistle safe for humans?

Milk thistle is generally considered safe and well-tolerated in humans, with only mild side effects like stomach upset and rare allergic reactions reported when taken within recommended doses. ^{1 2 5 6 7}

How is milk thistle treatment different for pediatric fatty liver disease?

Milk thistle is unique for pediatric fatty liver disease because it contains silymarin, which has antioxidant and liver-protecting properties, and there are currently no standard drug treatments for this condition. It has been used historically for various liver diseases, suggesting potential benefits, but more research is needed to confirm its effectiveness in children. ^{1 2 5 6 8}

What is the purpose of this trial?

Pediatric Fatty Liver disease is a growing problem in the United States and is expected to be the leading cause of Liver Transplantation in Adults in 20 years. Following lifestyle changes such as diet restrictions and exercise may be difficult to consistently maintain. The purpose of this study is to investigate alternative medical therapy with an herbal supplement called Milk Thistle (MT) which may improve fatty liver disease and would be easier to follow than diet and exercise.

Research Team

Thomas Sferra, MD

Principal Investigator

University Hospitals

Eligibility Criteria

This trial is for children with a condition called non-alcoholic fatty liver disease (NAFLD). They should not have other serious health issues. The study aims to find out if Milk Thistle, an herbal supplement, can help improve their liver health.

Inclusion Criteria

I am not pregnant, breastfeeding, or planning to become pregnant and will use two forms of birth control if of childbearing potential.

Evidence of Sonographic presence of hepatic steatosis with greater than 5% steatosis on Ultrasound or FibroScan (with a controlled attenuation parameter (CAP) score of 238 or greater) prior to start of trial starting

My liver biopsy showed signs of fatty liver disease.

Exclusion Criteria

I do not have a history of serious illnesses like cancer, immune diseases, or uncontrolled high blood pressure.

My diabetes is not under control, or my HbA1c is above 9%.

I have a history of heart or blood vessel problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Milk Thistle or placebo capsules based on weight by mouth once or twice daily

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Milk Thistle

Trial Overview The trial is testing the effectiveness of Milk Thistle compared to a placebo in improving NAFLD in kids. Participants will also undergo Fibroscan tests and be advised on lifestyle modifications like diet and exercise.

Participant Groups

Group I: Placebo Experimental Treatment 3 Interventions

Patients will be give 500mg capsule based on weight by mouth once or twice daily for 12 weeks.

Group II: Milk Thistle Experimental Treatment 3 Interventions

Patients will be given Milk Thistle capsules based on weight by mouth once or twice daily for 12 weeks.

Who Is Running the Clinical Trial?

Thomas J Sferra, MD

Lead Sponsor

Trials

1

Recruited

20+

University Hospitals Cleveland Medical Center

Lead Sponsor

Trials

348

Recruited

394,000+

Findings from Research

In a study using a validated animal model for NASH, milk thistle extract (ETHIS-094™) significantly reduced liver weight and liver-to-body weight ratio in mice, suggesting its potential effectiveness in treating liver fat accumulation.

The treatment with milk thistle also showed a decreasing trend in NAFLD activity score and steatosis scores, indicating its possible anti-steatosis effects, although these results were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo efficacy study of milk thistle extract (ETHIS-094™) in STAM™ model of nonalcoholic steatohepatitis. Pais, P., D'Amato, M.[2023]

Milk thistle (MT), particularly its active component silybin, has demonstrated various beneficial properties for liver health, including anti-inflammatory, antioxidant, and liver-regenerating effects, making it a potential therapeutic option for liver diseases.

Despite promising preclinical results, the current literature indicates a need for more well-designed randomized clinical trials to confirm the efficacy and safety of milk thistle preparations in treating liver conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Abenavoli, L., Izzo, AA., Milić, N., et al.[2023]

Silymarin, derived from milk thistle, has shown significant efficacy in treating non-alcoholic fatty liver disease (NAFLD) by reducing liver steatosis, ballooning, and fibrosis, as well as lowering aminotransferase levels in clinical studies.

Phase III trials indicate that silymarin is currently the best medication for NAFLD patients, offering similar effectiveness to insulin sensitizers but with fewer side effects, although challenges remain in its standardization and dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phytotherapy and NAFLD--from goals and challenges to clinical practice. Milosević, N., Milanović, M., Abenavoli, L., et al.[2023]

In a randomized trial of 99 patients with nonalcoholic steatohepatitis (NASH), silymarin did not significantly reduce the NAFLD activity score (NAS) by 30% or more compared to placebo, indicating limited efficacy in this primary outcome.

However, silymarin was associated with a significant reduction in liver fibrosis, with 22.4% of patients showing histological improvements compared to 6.0% in the placebo group, suggesting potential benefits for liver health despite the lack of impact on NAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. Wah Kheong, C., Nik Mustapha, NR., Mahadeva, S.[2018]

A new UHPLC-MS/MS method was developed and validated for accurately measuring six key flavonolignans from milk thistle in human serum, demonstrating high precision and sensitivity.

The extraction efficiency of the method ranged from 81% to 109%, with excellent linearity and low variability, making it a reliable tool for analyzing the hepatoprotective compounds in milk thistle supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Laboratory Validation of UHPLC-MS/MS Assays for Six Milk Thistle Flavonolignans in Human Serum. Muchiri, RN., van Breemen, RB.[2023]

In a case report involving a patient with non-alcoholic fatty liver disease (NAFLD) and overweight, silymarin (140 mg twice daily) effectively reduced liver enzyme activity, indicating its potential as a supportive treatment for NAFLD.

Silymarin demonstrated a good safety profile, suggesting it could be a promising intervention for normalizing liver function in patients with NAFLD, especially since no effective drug treatments are currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Silymarin treatment and reduction of liver enzyme levels in non-alcoholic fatty liver disease: a case report. Chantarojanasiri, T.[2023]

Milk thistle, particularly its active component silymarin, has shown protective effects on liver and kidney cells against toxins, including those from chemotherapy, and has demonstrated anti-inflammatory properties.

While considered safe and well-tolerated, with few side effects, more rigorous clinical trials are needed to fully assess silymarin's effectiveness in treating liver toxicity and various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the use of milk thistle (Silybum marianum). Post-White, J., Ladas, EJ., Kelly, KM.[2023]

Silymarin treatment in mice on a high-fat diet led to significant weight loss and reduced epididymal fat mass, indicating its potential effectiveness in combating diet-induced obesity.

Silymarin also improved liver health by decreasing liver enzyme levels (ALT and AST) and reducing inflammation, suggesting it may protect against liver damage and insulin resistance caused by high-fat diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice. Guo, Y., Wang, S., Wang, Y., et al.[2019]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

In vivo efficacy study of milk thistle extract (ETHIS-094™) in STAM™ model of nonalcoholic steatohepatitis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. [2023]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Phytotherapy and NAFLD--from goals and challenges to clinical practice. [2023]

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

A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Single Laboratory Validation of UHPLC-MS/MS Assays for Six Milk Thistle Flavonolignans in Human Serum. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Silymarin treatment and reduction of liver enzyme levels in non-alcoholic fatty liver disease: a case report. [2023]

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

Advances in the use of milk thistle (Silybum marianum). [2023]

8. England pubmed.ncbi.nlm.nih.gov

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice. [2019]