Licorice Botanical Dietary Supplements - Metabolism and Safety in Women

NCT03948243 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2019-0115
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Human safety studies will be carried out to test whether red clover botanical dietary supplements used by peri- and post-menopausal women are safe to use with Food and Drug Administration (FDA)-approved drugs. To test this, a red clover dietary supplement (previously tested in women at the University of Illinois at Chicago without any harmful effects) will be given with four selected FDA-approved drugs to determine if the Licorice supplement can increase or decrease how these medications are absorbed, metabolized and excreted by the human body. Preclinical studies predict that the licorice supplement might affect the metabolism or break down of these probe drugs.

Conditions

Food-drug Interaction

Keywords

Licorice

Outcome Measures

Primary Outcomes (1)

• 1. Area Under the Curve (AUC)

  Concentration of probe drugs from blood draws during the 14-day intervention will be used to calculate area under the (extrapolated) concentration-time curve to determine any changes compared to pre-intervention.

  baseline and 14 days

Secondary Outcomes (4)

• 1. Apparent Clearance

  baseline and 14 days

• 2. Peak Concentration

  baseline and 14 days

• 3. Time for Peak Concentration

  baseline and 14 days

• 4. Drug Half-life [Time Frame: baseline and 14 days]

  baseline and 14 days

Study Arms (1)

G.Glabra

EXPERIMENTAL

single arm

Dietary Supplement: Licorice; Drug: Alprazolam 2 MG; Drug: Caffeine 100 MG; Drug: Tolbutamide 250 mg; Drug: Dextromethorphan 30mg

Interventions

Licorice DIETARY_SUPPLEMENT

Experimental :G. glabra Licorice extract: 2 gelatin capsules (75 mg) per day for 14 days

Also known as: G. glabra

G.Glabra

Alprazolam 2 MG DRUG

probe substrate

Also known as: CYP3A4/5 substrate

G.Glabra

Caffeine 100 MG DRUG

probe substrate

Also known as: CYP1A2 substrate

G.Glabra

Tolbutamide 250 mg DRUG

probe substrate

Also known as: CYP2C9 substrate

G.Glabra

Dextromethorphan 30mg DRUG

probe substrate

Also known as: CYP2D6 substrate

G.Glabra

Eligibility Criteria

• Age: 40 Years - 79 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• healthy peri- and post-menopausal women ages 40 - 79
• non-smokers
• no-significant medical conditions as assessed by subject-reported medical history, physical examination and blood and urine chemistry screens
• no medical condition that requires chronic use of medication

You may not qualify if:

• known allergies or hypersensitivity to caffeine, dextromethorphan, sulfonylureas (tolbutamide), benzodiazepines, or licorice
• positive pregnancy test
• use of hormone therapy within 8 weeks of study initiation for oral agents, 4 weeks for transdermal or other topical agents
• use of caffeine products 7 days before study participation or during the study
• use of citrus products 7 days before study participation or during the study
• other prescription (with the exception of the Mirena® IUD) or non-prescription medicines within the 2 weeks prior to study initiation or during the study
• chronic diseases, such as inflammatory bowel disease, that could alter the absorption or metabolism of the probe substrates
• unwillingness to comply with study requirements
• current participation in another clinical trial
• CYP2D6 deficiency based on phenotyping at screening
• smoker
• licorice (whether as a botanical dietary supplement, candy, food, drink or otherwise) within the previous two weeks and during the study
• use of any dietary supplements within the last 2 weeks prior to study initiation and during the study
• extreme obesity (defined as \>40 BMI)
• alcohol or drug abuse

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• Oregon State University: collaborator

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Interventions

Glycyrrhiza glabra extract; Alprazolam; Caffeine; Tolbutamide; Dextromethorphan

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Xanthines; Alkaloids; Purinones; Purines; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Richard vanBreemen, PhD

  University of Illinois at Chicago

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 13, 2019
• Study Start: April 1, 2019
• Primary Completion: July 31, 2020
• Study Completion: April 22, 2022
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)