Assessing Goldenseal-drug Interactions Using a Probe Drug Cocktail Approach

NCT03772262 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 16620U54AT008909
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Goldenseal is a botanical natural product commonly used to self-treat symptoms of the common cold and many digestive disorders. Goldenseal products typically contain the isoquinoline alkaloids berberine, hydrastine, and hydrastinine. These constituents contain a methylenedioxyphenyl ring, a 'structural alert' that can lead to irreversible inhibition of drug metabolizing enzymes, particularly the cytochromes P450 (CYPs). Clinical studies involving healthy volunteers demonstrated that, compared to baseline (absence of goldenseal), CYP2D6 and CYP3A activities were reduced by 40-60% following treatment with goldenseal. Compared to the CYPs, the effects of goldenseal products on drug transporters are understudied, particularly in human subjects. Using a 'cocktail' consisting of 'probe' drug substrates for CYP3A and various transporters, the effects of goldenseal on the pharmacokinetics of each probe drug will be examined in healthy volunteers. Results will provide useful information about the risk of co-consuming goldenseal with additional drugs that are substrates for transporters.

Conditions

Interaction Drug Food

Keywords

Pharmacokinetics; Goldenseal; Metformin; Furosemide; Rosuvastatin; Midazolam; Natural product

Outcome Measures

Primary Outcomes (1)

• midazolam AUC ratio (treatment/control)

  ratio of the area under of the plasma concentration time curve (AUC) of midazolam in the presence to absence of goldenseal

  0-96 hours

Secondary Outcomes (1)

• midazolam Cmax ratio (treatment/control)

  0-96 hours

Study Arms (2)

Control

EXPERIMENTAL

Study subjects will be administered a single dose of midazolam syrup (2.5 mg), metformin solution (50 mg), furosemide solution (1 mg), and one rosuvastatin tablet (10 mg) by mouth. Plasma will be collected from 0-96 hours. Urine will be collected from 0-24 hours.

Drug: Metformin; Drug: Furosemide; Drug: Midazolam oral solution; Drug: Rosuvastatin Oral Tablet

Treatment

EXPERIMENTAL

Study subjects will be administered goldenseal 2 capsules (500 mg each) three times daily for 5 days. On day 6, subjects will be administered goldenseal 2 capsules (500 mg each), a single dose of midazolam syrup (2.5 mg), metformin solution (50 mg), furosemide solution (1 mg), and one tablet (10 mg) rosuvastatin. Goldenseal 2 capsules (500 mg each) will be administered approximately 4 and 8 hours later. Plasma will be collected from 0-96 hours. Urine will be collected from 0-24 hours.

Dietary Supplement: goldenseal; Drug: Metformin; Drug: Furosemide; Drug: Midazolam oral solution; Drug: Rosuvastatin Oral Tablet

Interventions

goldenseal DIETARY_SUPPLEMENT

Oral 500 mg capsules

Treatment

Metformin DRUG

Oral solution

Control; Treatment

Furosemide DRUG

Oral solution

Control; Treatment

Midazolam oral solution DRUG

Oral syrup

Control; Treatment

Rosuvastatin Oral Tablet DRUG

Oral tablet

Control; Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to participate in the study (time, transportation, etc.)
• Ability to understand the informed consent form
• Men and women aged from 18 to 65 years
• Willingness to abstain from alcohol and caffeinated beverages for the evening prior to and during each in-patient study day
• Willingness to abstain from citrus juices and other dietary supplements for the duration of the study

You may not qualify if:

• Any current major illness or chronic illness including but not limited to kidney disease, hepatic disease, diabetes mellitus, hypertension, coronary artery disease, chronic obstructive pulmonary disease, previous stroke or embolic disease history, cancer, and HIV/AIDS
• History of allergy to goldenseal, midazolam, furosemide, metformin, or rosuvastatin
• History of anemia or any other significant hematologic disorder
• History of renal failure or lactic acidosis (metformin)
• History of apnea (midazolam)
• History of heart failure, electrolyte imbalance (furosemide)
• History of hypotension (goldenseal)
• History of drug or alcohol addiction or major psychiatric illness
• Women who are intending to become pregnant within the next three months, are currently pregnant, or are currently breastfeeding
• Out-of-range clinical laboratory value that the study physician considers participation in the study a health risk
• Taking concomitant medications, both prescription and non-prescription (including herbal/natural products) known to alter the pharmacokinetics or pharmacodynamics of midazolam, furosemide, metformin, or rosuvastatin.

Sponsors & Collaborators

• Washington State University: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

Washington State University

Spokane, Washington, 99202, United States

Location

MeSH Terms

Interventions

Metformin; Furosemide; Midazolam; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Sulfanilamides; Sulfonamides; Amides; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

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

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: December 11, 2018
• Study Start: April 5, 2018
• Primary Completion: November 30, 2018
• Study Completion: March 31, 2019
• Last Updated: April 28, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)