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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Milk Thistle, an herbal supplement, can help treat Pediatric Fatty Liver Disease. This condition is becoming more common in the U.S. and could lead to serious liver issues in adulthood. Participants will take either Milk Thistle or a placebo (a sugar pill) to assess its impact on liver health. The trial seeks participants diagnosed with non-alcoholic fatty liver disease who experience symptoms like being overweight or having a family history of liver issues. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Milk Thistle is likely to be safe for children with fatty liver disease?

Research has shown that Milk Thistle, also known as silymarin, is generally safe for individuals with liver problems. In studies, participants with liver diseases reported few side effects when using Milk Thistle. For instance, one study found it improved liver function in children with liver issues without causing major side effects. Another study confirmed its safety for individuals with non-alcoholic fatty liver disease, with only a few negative reports.

In summary, Milk Thistle appears to be a safe choice for those with liver conditions and is well-tolerated by both adults and children. ^{1 2 3 4 5}

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

Unlike the standard treatments for pediatric fatty liver disease, which often focus on lifestyle changes like diet and exercise, Milk Thistle offers a different approach. This herbal remedy is thought to work through its active ingredient, silymarin, which may have antioxidant and anti-inflammatory properties. Researchers are excited about its potential to directly target liver health, offering a natural and potentially safer alternative to existing options. Additionally, Milk Thistle's use in capsule form based on weight provides a simple and convenient administration method for children.

What evidence suggests that Milk Thistle might be an effective treatment for pediatric fatty liver disease?

Research has shown that milk thistle, particularly its active component silymarin, might help treat non-alcoholic fatty liver disease (NAFLD). Studies indicate that silymarin can reduce liver fat and swelling, which are major issues in NAFLD. In children and teens, silymarin improved liver function and reduced fat buildup in the liver. It also helps control energy use in the body and reduces liver damage. In this trial, participants will receive either milk thistle or a placebo to evaluate its effectiveness in managing fatty liver disease. Overall, these findings suggest that milk thistle could be a promising option for managing fatty liver disease. ^{1 2 6 7 8}

Who Is on the Research Team?

Thomas Sferra, MD

Principal Investigator

University Hospitals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06477146

NCT06477146 | Milk Thistle Clinical Trial in Pediatric NAFLD 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3612568/

Silymarin in non alcoholic fatty liver disease In conclusion, the results obtained indicate that silymarin seems to be effective in reducing the biochemical and ultrasonographic changes induced by NAFLD.

3. researchgate.net researchgate.net/publication/322366067_The_effect_of_silymarin_on_non-alcoholic_fatty_liver_disease_of_children/fulltext/5d0c30e592851cf4403e46eb/The-effect-of-silymarin-on-non-alcoholic-fatty-liver-disease-of-children.pdf

The-effect-of-silymarin-on-non-alcoholic-fatty-liver-disease- ... Conclusion: Silymarin can improve fatty infiltration of liver and liver function in children and adolescents. Silybum marianum with high polyphenolic content ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1665268123002776

Administration of silymarin in NAFLD/NASH: A systematic ... Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients.

5. withpower.com withpower.com/trial/phase-2-liver-diseases-7-2024-3991b

Milk Thistle for Pediatric Fatty Liver Disease Some studies have demonstrated that silymarin can improve liver conditions by reducing liver fat, inflammation, and damage.

6. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1295816/full

Effect of oral silymarin on liver function in pediatric acute ... The results of the present study showed that in pediatric patients with ALL, silymarin intake improves liver function.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024074760

Milk thistle protects against non-alcoholic fatty liver disease ... The purpose of this study was to evaluate the ability of milk thistle to protect rabbits from the toxicity of oxidized tallow (OT).

8. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07210-6

Efficacy of silymarin in patients with non-alcoholic fatty liver ... Silybum marianum has shown good tolerance and safety, with limited adverse effects reported in liver disease patients.