Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) to Treat Alcohol-Associated Liver Disease
Primary Purpose
Alcohol-Related Disorders
Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dihydromyricetin
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol-Related Disorders
Eligibility 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
Sites / Locations
- University of Southern California
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Arm Description
DHM 300mg x1 dose
DHM 900mg x1 dose
DHM 300mg x1 dose + Lysine 140mg x1 dose
DHM 900mg x1 dose + Lysine 420mg x1 dose
Outcomes
Primary Outcome Measures
Pharmacokinetics
serum DHM metabolites will be performed using MRM mass
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
Secondary Outcome Measures
Full Information
NCT ID
NCT05623501
First Posted
November 11, 2022
Last Updated
November 11, 2022
Sponsor
University of Southern California
1. Study Identification
Unique Protocol Identification Number
NCT05623501
Brief Title
Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) to Treat Alcohol-Associated Liver Disease
Official Title
Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) to Treat Alcohol-Associated Liver Disease
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2022 (Anticipated)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Southern California
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol-Related Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
DHM 300mg x1 dose
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
DHM 900mg x1 dose
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
DHM 300mg x1 dose + Lysine 140mg x1 dose
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
DHM 900mg x1 dose + Lysine 420mg x1 dose
Intervention Type
Drug
Intervention Name(s)
Dihydromyricetin
Intervention Description
Dose-escalation and lysine preparation
Primary Outcome Measure Information:
Title
Pharmacokinetics
Description
serum DHM metabolites will be performed using MRM mass
Time Frame
-0.5 (pre-dose), 0 (1st dose), 0.5, 1, 2, 4, 6, 8 (2nd dose), 12, and 24 hours post-dose.
Title
Adverse Events
Description
The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 will be used to assess and grade AE severity
Time Frame
24 hours post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brian Lee, MD
Phone
323-442-5576
Email
brian.lee@med.usc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian Lee, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brian Lee, MD
Phone
323-442-5576
Email
brian.lee@med.usc.edu
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Undecided
Learn more about this trial
Phase I, Dose-Escalation Study of Dihydromyricetin (DHM) to Treat Alcohol-Associated Liver Disease
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