DHM for Liver Disease

Overseen By Brian Lee, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Southern California

Must not be taking: CYP3A4 drugs

Disqualifiers: Advanced liver disease, HIV, others

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

Compensation: Varies

Number of Visits: 24

Duration: 1 day

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking drugs that affect CYP3A4 (a liver enzyme), you will need to stop taking them to participate in this trial.

What data supports the effectiveness of the drug dihydromyricetin for liver disease?

Research shows that dihydromyricetin (DHM) can help protect the liver from damage caused by chemicals and alcohol, improve liver cell regeneration, and reduce fat buildup in the liver. It also has anti-inflammatory and antioxidant properties, which may help treat liver diseases like nonalcoholic fatty liver disease (NAFLD) and liver cancer. ^{1 2 3 4 5}

Is Dihydromyricetin (DHM) safe for human use?

The safety of herbal and dietary supplements, including those containing Dihydromyricetin (DHM), can be uncertain as they have been associated with liver injury in some cases. While DHM itself is not specifically mentioned, similar supplements have been linked to liver problems, so caution is advised. ^{6 7 8 9 10}

How does the drug Dihydromyricetin (DHM) differ from other treatments for liver disease?

Dihydromyricetin (DHM) is unique because it is a natural compound with strong antioxidant and anti-inflammatory properties, which helps protect the liver from damage caused by alcohol and other toxins. Unlike standard treatments, DHM also regulates lipid and glucose metabolism, and it has shown potential in reducing liver cancer cell growth and improving liver fibrosis, making it a promising option for various liver conditions. ^{1 4 11 12 13}

What is the purpose of this trial?

The current proposal is designed as a first-in-human Phase 1 open-label, dose-escalation study to assess the safety, pharmacokinetics, and the maximum tolerated dose of DHM among healthy volunteers using a purified form of DHM from a local cGMP compliant source (Master Herbs, Inc).

Research Team

Brian Lee, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for healthy volunteers aged 18-60 with no history of alcohol use disorder or liver disease. Participants must weigh over 50kg and not have acute illnesses, pancreatic/biliary diseases, advanced liver conditions, HIV, other liver diseases, or be pregnant. They also shouldn't be on drugs affecting CYP3A4 enzymes.

Inclusion Criteria

No prior medical history of alcohol use disorder or alcohol-associated liver disease

Exclusion Criteria

Pregnancy

I have had pancreatic or biliary disease.

My liver disease is in an advanced stage.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of DHM, with pharmacokinetic and safety assessments

1 day

Multiple visits within 24 hours for PK and safety assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Dihydromyricetin

Trial Overview The study tests the safety and appropriate dosage levels of Dihydromyricetin (DHM), a compound being explored to treat Alcohol-Associated Liver Disease. It's an open-label trial where everyone gets DHM in increasing doses to find the highest dose that's safe without severe side effects.

Participant Groups

Group I: Cohort 4 Experimental Treatment 1 Intervention

DHM 900mg x1 dose + Lysine 420mg x1 dose

Group II: Cohort 3 Experimental Treatment 1 Intervention

DHM 300mg x1 dose + Lysine 140mg x1 dose

Group III: Cohort 2 Experimental Treatment 1 Intervention

DHM 900mg x1 dose

Group IV: Cohort 1 Experimental Treatment 1 Intervention

DHM 300mg x1 dose

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Findings from Research

Drug-induced liver injury (DILI) and herb-induced liver injury are increasingly recognized as significant issues, necessitating careful diagnosis and management, particularly through drug discontinuation and therapy reconciliation.

Post-marketing databases are crucial for detecting DILI risks, highlighting the need for improved pre-clinical testing and ongoing surveillance, with a focus on direct oral anticoagulants and herbal supplements as key areas for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk. Raschi, E., De Ponti, F.[2020]

A new hepatotoxicity database was created using the FDA's adverse event reporting system, analyzing 2029 unique drugs and 13,555 drug-adverse event combinations to better predict drug-induced liver injury (DILI).

The study developed a classification scheme that effectively distinguishes between drugs that are likely to cause liver damage and those that are not, which can enhance the safety assessment of new medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction and analysis of a human hepatotoxicity database suitable for QSAR modeling using post-market safety data. Zhu, X., Kruhlak, NL.[2019]

References

1. France pubmed.ncbi.nlm.nih.gov

Molecular mechanisms and therapeutic implications of dihydromyricetin in liver disease. [2022]

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

Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Molecular mechanism and therapeutic significance of dihydromyricetin in nonalcoholic fatty liver disease. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Dihydromyricetin ameliorated nonalcoholic steatohepatitis in mice by regulating the composition of serous lipids, bile acids and ileal microflora. [2023]

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

Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression. [2021]

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

Botanicals and Hepatotoxicity. [2019]

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

Liver injury from herbal and dietary supplements. [2022]

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

Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk. [2020]

9. Ireland pubmed.ncbi.nlm.nih.gov

Construction and analysis of a human hepatotoxicity database suitable for QSAR modeling using post-market safety data. [2019]

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

Herbal hepatotoxicity. [2016]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Dihydromyricetin inhibits Hepatitis B virus replication by activating NF-κB, MAPKs, and autophagy in HepG2.2.15 cells. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway. [2021]