Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) to Treat Alcohol-Associated Liver Disease

Alcohol-Related Disorders Clinical Trial

Official title:

Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) to Treat Alcohol-Associated Liver Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05623501
• Other study ID #: 22-00428
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: January 1, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: University of Southern California
• Contact: Brian Lee, MD
• Phone: 323-442-5576
• Email: brian.lee[@]med.usc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

Dihydromyricetin (DHM), a bioactive flavonoid from an edible plant (ampelopsis grossedentata), is reported to have multiple protective effects against chemical-induced liver injuries. For example, the antioxidant activity and cellular metabolic protective effects of DHM may act via the AMP kinase (AMPK) and nicotinamide adenine dinucleotide (NAD+)-dependent Sirtuin (Sirt)-1 energy regulating pathway. Furthermore, there is accumulating evidence supporting the use of DHM for the treatment of alcohol use disorder and the possible reduction/prevention of alcohol-associated liver disease in animal models. DHM may represent a novel approach to counteract alcohol-induced liver damage and promote alcohol metabolism via changes in hepatocellular bioenergetics and mitochondrial biogenesis driven by the AMPK/Sirt-1/PGC-1α axis. These preclinical data suggest the potential of DHM as a novel therapeutic agent in alcohol-related diseases. However, further study in humans is warranted. While DHM has been used for herbal tea in traditional Chinese medicine for hundreds of years, and there has been a small clinical trial using DHM in China among individuals with non-alcoholic fatty liver disease, there have been no controlled human studies published that have assessed the safety, pharmacokinetics, or optimal dosing of DHM in humans. DHM is marketed as a dietary supplement in the United States and is not regulated by the Food and Drug Administration (FDA) as a drug. Because the FDA has little control over the quality of herbal products such as DHM, it is necessary to quantitatively estimate the potentially active ingredients and the pharmacokinetic (PK) profile with oral administration. 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• No prior medical history of alcohol use disorder or alcohol-associated liver disease
• Between 18-60 years old

Exclusion Criteria:

• Weight below 50kg.
• Advanced liver disease
• Other acute liver diseases
• HIV co-infection
• History of pancreatic or biliary disease
• Acute illness that would interfere with drug absorption
• Pregnancy
• Participants who are currently taking drugs with CYP3A4 effects

Related Conditions & MeSH terms

• Alcohol-Related Disorders
• Liver Diseases

Intervention

Drug:
• Dihydromyricetin
Dose-escalation and lysine preparation

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics	serum DHM metabolites will be performed using MRM mass	-0.5 (pre-dose), 0 (1st dose), 0.5, 1, 2, 4, 6, 8 (2nd dose), 12, and 24 hours post-dose.
Primary	Adverse Events	The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 will be used to assess and grade AE severity	24 hours post-dose