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

NCT05623501 | Not Yet Recruiting Phase 1

• 1 other identifier: 22-00428
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Alcohol-Related Disorders

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic of DHM

  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), 10, and 24 hours post-dose.

• 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

Study Arms (4)

Cohort 1

EXPERIMENTAL

DHM 300mg x1 dose

Drug: Dihydromyricetin

Cohort 2

EXPERIMENTAL

DHM 900mg x1 dose

Drug: Dihydromyricetin

Cohort 3

EXPERIMENTAL

DHM 300mg x1 dose + Lysine 140mg x1 dose

Drug: Dihydromyricetin

Cohort 4

EXPERIMENTAL

DHM 900mg x1 dose + Lysine 420mg x1 dose

Drug: Dihydromyricetin

Interventions

Dihydromyricetin DRUG

Dose-escalation and lysine preparation

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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
• FIB-4 Index \> 1.30
• History of Alcohol Use Disorder (AUD) determined by score \> 8 on AUDIT questionnaire

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

University of Southern California

Los Angeles, California, 90089, United States

Location

MeSH Terms

Conditions

Alcohol-Related Disorders

Interventions

dihydromyricetin

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Brian Lee, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian Lee, MD

CONTACT

323-442-5576; brian.lee@med.usc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: 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 as liquid suspension. Cohort 2 will consist of three healthy volunteers who will receive DHM in two doses of 900 mg as liquid suspension. 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, requiring two consecutive days of visits to research clinic. Evaluations will be taken at uniform intervals.

Study Record Dates

• First Submitted: November 11, 2022
• First Posted: November 21, 2022
• Study Start: September 15, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)