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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05623501
Recruitment Status : Not yet recruiting
First Posted : November 21, 2022
Last Update Posted : November 21, 2022
Sponsor:
Information provided by (Responsible Party):
Brian P. Lee, University of Southern California

Brief 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).

Condition or disease Intervention/treatment Phase
Alcohol-Related Disorders Drug: Dihydromyricetin Phase 1

Detailed 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a single-center dose-escalation study. A total of 12 participants are planned and will be divided into 4 cohorts with 3 participants per cohort. Cohort 1 will consist of three healthy volunteers who will receive DHM in two doses of 300 mg. Cohort 2 will consist of three healthy volunteers who will receive DHM in two doses of 900 mg. Cohort 3 will consist of three healthy volunteers who will receive DHM in two 50mL PO solution doses of 300 mg plus 140mg L-lysine. Cohort 4 will consist of three healthy volunteers who will receive DHM in two 50mL PO solution doses of 900 mg plus 420mg L-lysine. Each participant will be administered the study drug during a 24-hour period. Evaluations will be taken at uniform intervals.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) to Treat Alcohol-Associated Liver Disease
Estimated Study Start Date : December 1, 2022
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases

Arm Intervention/treatment
Experimental: Cohort 1
DHM 300mg x1 dose
Drug: Dihydromyricetin
Dose-escalation and lysine preparation

Experimental: Cohort 2
DHM 900mg x1 dose
Drug: Dihydromyricetin
Dose-escalation and lysine preparation

Experimental: Cohort 3
DHM 300mg x1 dose + Lysine 140mg x1 dose
Drug: Dihydromyricetin
Dose-escalation and lysine preparation

Experimental: Cohort 4
DHM 900mg x1 dose + Lysine 420mg x1 dose
Drug: Dihydromyricetin
Dose-escalation and lysine preparation




Primary Outcome Measures :
  1. Pharmacokinetics [ Time Frame: -0.5 (pre-dose), 0 (1st dose), 0.5, 1, 2, 4, 6, 8 (2nd dose), 12, and 24 hours post-dose. ]
    serum DHM metabolites will be performed using MRM mass

  2. Adverse Events [ Time Frame: 24 hours post-dose ]
    The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 will be used to assess and grade AE severity



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05623501


Contacts
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Contact: Brian Lee, MD 323-442-5576 brian.lee@med.usc.edu

Locations
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United States, California
University of Southern California
Los Angeles, California, United States, 90089
Contact: Brian Lee, MD    323-442-5576    brian.lee@med.usc.edu   
Sponsors and Collaborators
University of Southern California
Investigators
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Principal Investigator: Brian Lee, MD University of Southern California
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Responsible Party: Brian P. Lee, Assistant Professor of Medicine, University of Southern California
ClinicalTrials.gov Identifier: NCT05623501    
Other Study ID Numbers: 22-00428
First Posted: November 21, 2022    Key Record Dates
Last Update Posted: November 21, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Diseases
Alcohol-Related Disorders
Digestive System Diseases
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders