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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and optimal dosage of a compound called dihydromyricetin (DHM) for potential liver disease treatment. Researchers are testing various doses of DHM, both alone and with lysine, to understand how the body processes it and to determine the maximum safe dose. The study is open to healthy volunteers without a history of liver disease or alcohol use disorder. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that Dihydromyricetin (DHM) is generally safe for people. According to a source from the NIH, early trials reported no major side effects from DHM. It is often used for liver health and has shown potential in protecting against liver damage in animal studies.

DHM is also being tested with Lysine, an amino acid that helps the body build proteins. While specific human data on this combination is not yet available, past studies have found DHM alone to be safe. However, like many herbal supplements, more research is needed to fully understand its safety in humans.

This trial is in the early stages, focusing mainly on assessing the treatment's safety. Although human data is limited, DHM's positive results in other studies are promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Dihydromyricetin (DHM) for liver disease because it offers a novel approach compared to standard treatments like antiviral medications and lifestyle changes. DHM is unique because it is derived from natural sources and is being tested both alone and in combination with lysine, which could enhance its effects. Unlike traditional treatments that often focus on managing symptoms or controlling disease progression, DHM might provide a more direct protective effect on liver cells. This approach could lead to faster and potentially more sustainable improvements in liver health.

What evidence suggests that this trial's treatments could be effective for liver disease?

Research suggests that dihydromyricetin (DHM) may benefit liver health. In a small study involving individuals with nonalcoholic fatty liver disease, DHM improved certain liver health indicators in their blood. It also reduced liver inflammation and fat buildup. Animal studies indicate that DHM can help the liver recover from alcohol-related damage. In this trial, participants will receive different doses of DHM, with some groups also receiving lysine. Combined with lysine, DHM might offer extra protection to liver cells by reducing damage and inflammation. These findings suggest DHM could help with liver issues, but more research in humans is needed. ^{1 6 7 8 9}

Who Is on the Research Team?

Brian Lee, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK594407/

Dihydromyricetin - LiverTox - NCBI Bookshelf - NIH

In one small placebo-controlled trial of DHM in patients with nonalcoholic fatty liver, DHM resulted in greater improvements in serum ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0741832920302901

Alcohol

Dihydromyricetin (DHM), a bioactive flavonoid, improved mitochondrial outcomes in the liver of male C57BL/6J mice after chronic alcohol feeding.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05623501

Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) ...

These preclinical data suggest the potential of DHM as a novel therapeutic agent in alcohol-related diseases. However, further study in humans is warranted.

4.

nutritionandmetabolism.biomedcentral.com

nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-021-00589-6

Dihydromyricetin ameliorates liver fibrosis via inhibition of ...

A randomized controlled trial further indicated that DHM supplementation significantly decreased hepatic steatosis and suppressed inflammation ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11729546/

Dihydromyricetin Alleviates Non-Alcoholic Fatty Liver Disease ...

The results showed that DHM treatment significantly reduced serum levels of LPS, IL-1β, and TNF-α, decreasing the liver expression of TLR4 and NF-κB p65.

6.

alzdiscovery.org

alzdiscovery.org/uploads/cognitive_vitality_media/Dihydromyricetin.pdf

Dihydromyricetin

DHM has been shown to protect against both alcoholic and non-alcoholic associated fatty liver disease in rodent models by reducing hepatic inflammation, ...

7.

consumerlab.com

consumerlab.com/answers/dihydromyricetin-dhm-does-it-help-and-is-it-safe/dhm-supplement/

Dihydromyricetin (DHM) - Safety & Effectiveness

Dihydromyricetin (DHM) is promoted for liver health, diabetes, lowering cholesterol, and as a hangover remedy. Find out if it works and ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05623501

Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) ...

These preclinical data suggest the potential of DHM as a novel therapeutic agent in alcohol-related diseases. However, further study in humans is warranted.

9.

sciencedirect.com

sciencedirect.com/science/article/pii/S0753332221007095

Molecular mechanisms and therapeutic implications of ...

Dihydromyricetin exhibits prominent therapeutic effects on various liver diseases. •. Dihydromyricetin alleviates acute hepatic injury and hepatocyte necrosis, ...