Effects of Kudzu Root (Gegen) on Drug-Metabolizing Enzymes and Blood Clotting in Healthy Volunteers

NCT07823140 | Completed Phase 1

• 1 other identifier: ZUO-P19-004
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: The purpose of this study is to understand how the traditional herbal medicine kudzu root (Gegen, Radix Puerariae lobatae) affects the activity of drug metabolizing enzymes in the body, and whether this could lead to interactions with other medicines. Background: Many medicines are broken down in the body by enzymes called cytochrome P450 (CYP) enzymes. Preclinical data suggest that Gegen can inhibit CYP enzymes, which may lead to herb-drug interactions; however, robust clinical evidence in humans remains insufficient. Participants: This study recruited 56 healthy Chinese adults, who were randomly assigned to parallel low and high dose Gegen groups; 52 participants finished the study. Interventions: Participants took a mixture of probe medicines known as a CYP probe cocktail to measure baseline CYP enzyme activity. After receiving either low or high dose Gegen, they received the probe cocktail again to detect changes in enzyme activity. Blood samples were collected to test the probe medicines, their breakdown products, and markers for blood clotting and blood vessel health. Outcome Measures: Primary outcomes include changes in blood levels and metabolic ratios of probe medicines. These values reflect differences in CYP enzyme activity with and without Gegen, and are compared across low and high dose groups. Hypothesis: The study hypothesized that Gegen alters CYP enzyme activity, and that the magnitude of this effect varies with Gegen dose.

Conditions

Herb-drug Interactions

Keywords

Kudzu root; Gegen; Pueraria lobata; Herb-drug interaction; Cytochrome P450; CYP2C19; Probe drug cocktail; Traditional Chinese medicine

Outcome Measures

Primary Outcomes (9)

• Change in CYP1A2 phenotypic activity

  Plasma concentrations of caffeine and its metabolite paraxanthine were quantified by validated LC-MS/MS. CYP1A2 activity was expressed as the AUC0-t derived metabolite-to-parent ratio (unit of measure: ratio).

  Session I (baseline) and Session II (after 14 days of Gegen administration); within each session, blood samples were collected at pre-dose (0 hour) and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after dosing of cocktail probe drugs.

• Change in CYP2B6 phenotypic activity

  Plasma concentrations of efavirenz and its metabolite 8-Hydroxy-efavirenz were quantified by validated LC-MS/MS. CYP1A2 activity was expressed as the AUC0-t derived metabolite-to-parent ratio (unit of measure: ratio).

  Session I (baseline) and Session II (after 14 days of Gegen administration); within each session, blood samples were collected at pre-dose (0 hour) and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after dosing of cocktail probe drugs.

• Change in CYP2C9 phenotypic activity

  Plasma concentrations of losartan and its metabolite E-3174 were quantified by validated LC-MS/MS. CYP1A2 activity was expressed as the AUC0-t derived metabolite-to-parent ratio (unit of measure: ratio).

  Session I (baseline) and Session II (after 14 days of Gegen administration); within each session, blood samples were collected at pre-dose (0 hour) and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after dosing of cocktail probe drugs.

• Change in CYP2C19 phenotypic activity

  Plasma concentrations of omeprazole and its metabolite 5-Hydroxy-omeprazole were quantified by validated LC-MS/MS. CYP1A2 activity was expressed as the AUC0-t derived metabolite-to-parent ratio (unit of measure: ratio).

  Session I (baseline) and Session II (after 14 days of Gegen administration); within each session, blood samples were collected at pre-dose (0 hour) and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after dosing of cocktail probe drugs.

• Change in CYP2D6 phenotypic activity

  Plasma concentrations of metoprolol and its metabolite α-Hydroxy-metoprolol were quantified by validated LC-MS/MS. CYP1A2 activity was expressed as the AUC0-t derived metabolite-to-parent ratio (unit of measure: ratio).

  Session I (baseline) and Session II (after 14 days of Gegen administration); within each session, blood samples were collected at pre-dose (0 hour) and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after dosing of cocktail probe drugs.

• Change in CYP3A4 phenotypic activity

  Plasma concentrations of midazolam and its metabolite 1'-Hydroxy-midazolam were quantified by validated LC-MS/MS. CYP1A2 activity was expressed as the AUC0-t derived metabolite-to-parent ratio (unit of measure: ratio).

  Session I (baseline) and Session II (after 14 days of Gegen administration); within each session, blood samples were collected at pre-dose (0 hour) and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after dosing of cocktail probe drugs.

• Change in thromboxane B2 concentration

  Plasma concentration of thromboxane B2, a biomarker of platelet activation and coagulation, was quantified by enzyme-linked immunosorbent assay (unit of measure: ng/mL).

  Blood samples collected at pre-dose (0 hour) in Session I (baseline) and 72 hours post-cocktail-dose in Session II (after 14 days of Gegen dosing)

• Change in soluble thrombomodulin concentration

  Plasma concentration of soluble thrombomodulin, a biomarker of endothelial function, was quantified by enzyme-linked immunosorbent assay (unit of measure: ng/mL).

  Blood samples collected at pre-dose (0 hour) in Session I (baseline) and 72 hours post-cocktail-dose in Session II (after 14 days of Gegen dosing)

• Change in prothrombin time

  Plasma prothrombin time, a coagulation parameter, was measured by standard clotting assay on an automated coagulometer (unit of measure: seconds).

  Blood samples collected at pre-dose (0 hour) in Session I (baseline) and 72 hours post-cocktail-dose in Session II (after 14 days of Gegen dosing)

Secondary Outcomes (1)

• Incidence of adverse events

  From enrolment until the final visit (72 hours after the Session II probe cocktail administration)

Study Arms (2)

Low dose Gegen

EXPERIMENTAL

Participants received the low-dose (3.3 g) Gegen regimen for 14 days; the six-probe drug cocktail was administered once before (Session I, baseline) and once after (Session II) Gegen dosing for CYP phenotyping.

Drug: Arm 1: Radix Puerariae lobatae (Gegen); Drug: Arm 1: Six-probe drug cocktail

High dose Gegen

EXPERIMENTAL

Participants received the high-dose (5 g) Gegen regimen for 14 days; the six-probe drug cocktail was administered once before (Session I, baseline) and once after (Session II) Gegen dosing for CYP phenotyping.

Drug: Arm 2: Radix Puerariae lobatae (Gegen); Drug: Arm 2: Six-probe drug cocktail

Interventions

Arm 1: Radix Puerariae lobatae (Gegen) DRUG

Granules of the dried root of Pueraria lobata (listed in the Hong Kong Chinese Materia Medica Standards; Chinese Pharmacopoeia monograph Radix Puerariae Lobatae).

Also known as: Puerariae Lobatae Radix, Kudzu Root, Lobed Kudzuvine Root

Low dose Gegen

Arm 1: Six-probe drug cocktail DRUG

Single oral dose of a cocktail comprising caffeine (CYP1A2), efavirenz (CYP2B6), losartan (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), and midazolam (CYP3A4).

Also known as: caffeine, efavirenz, losartan, omeprazole, metoprolol, midazolam

Low dose Gegen

Arm 2: Radix Puerariae lobatae (Gegen) DRUG

Granules of the dried root of Pueraria lobata (listed in the Hong Kong Chinese Materia Medica Standards; Chinese Pharmacopoeia monograph Radix Puerariae Lobatae).

Also known as: Puerariae Lobatae Radix, Kudzu Root, Lobed Kudzuvine Root

High dose Gegen

Arm 2: Six-probe drug cocktail DRUG

Single oral dose of a cocktail comprising caffeine (CYP1A2), efavirenz (CYP2B6), losartan (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), and midazolam (CYP3A4).

Also known as: caffeine, efavirenz, losartan, omeprazole, metoprolol, midazolam

High dose Gegen

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and non-pregnant female Chinese subjects, 20 - 45 years of age.
• Body weight within 15% of ideal weight (according to the Metropolitan InsuranceCompany Bulletin).
• Accessible vein for blood sampling.
• High probability for compliance and completion of the study.
• Female subjects who are surgically sterile or post-menopausal. Or female subjects of child bearing potential agree to practice abstinence or take effective contraceptive methods (e.g. non-hormonal intra-uterine device, consistent condom plus spermicide use or consistent cervical cap with spermicide) from the start of screening until two weeks of last dose administration to prevent pregnancy.
• Male subjects agree to practice abstinence or take effective contraceptive method (refer to the aforementioned) from the start of screening until two weeks of last dose administration to prevent his partner pregnant.
• Subjects agree to abstain from any prescription or non-prescription medications 2 weeks before the first dosing and throughout the study (except those allowed based on investigator's judgement).
• Have signed the written informed consent to participate in the study.

You may not qualify if:

• Clinically significant hepatic, renal, biliary, cardiovascular, gastrointestinal, haematological and other chronic and acute diseases within 3 months prior to the study.
• Clinically significant abnormality in physical examination, ECG evaluation, urine test, blood chemistry or haematological test.
• Tobacco uses in any forms.
• Positive results of hepatitis B.
• Regular consumer of alcohol (on average more than one drink per day within 1 month prior to the start of first dosing).
• Consumer of Asian vegetables, fruits or other herb medicine which are known to contain moderate to high levels of furanocoumarins, such as grapefruit juice, or herbal teas that naturally contain coumadin or coumadin-like substances such as Chamomile tea.
• Have lost or donate more than 350 ml blood donation within 4 weeks prior to the start of the study.
• Administer any prescription or non-prescription medications which is likely to be required during the course of the study (except those allowed based on investigator's judgement).
• Treatment of Gegen or the studied probe drugs (caffeine, losartan, omeprazole, metoprolol, midazolam, efavirenz) within 2 weeks before the study.
• Volunteer in any clinical drug study within 1 month prior to this study
• History of allergy or hypersensitivity to Gegen or the studied probe drugs (caffeine, losartan, omeprazole, metoprolol, midazolam, efavirenz) and other drugs in its class.
• History of drug abuse in any form.
• Genetics of the studied six CYPs revealed no enzyme activity (homozygous), including following genetic variants: CYP2C9\*25, CYP2C19\*2, CYP2C19\*3, CYP2C19\*4, CYP2C19\*35, CYP2D6\*4, CYP2D6\*6, CYP3A4\*20.
• Female subjects who are breastfeeding or pregnancy.
• Subjects who are considered not suitable in participating the study due to other unfavourable factors determined by investigators.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

The Chinese University of Hong Kong Phase 1 Clinical Trial Centre

Hong Kong, Hong Kong

Location

MeSH Terms

Interventions

Caffeine; efavirenz; Losartan; Omeprazole; Metoprolol; Midazolam

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetrazoles; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Benzimidazoles; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Benzodiazepines; Benzazepines

Study Officials

• Zhong Zuo, PhD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 4, 2026
• First Posted: September 16, 2026
• Study Start: August 8, 2022
• Primary Completion: April 21, 2023
• Study Completion: April 28, 2023
• Last Updated: September 23, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)