Hop Botanical Dietary Supplements - Metabolism and Safety in Women

• ClinicalTrials.gov Identifier: NCT02848430
• Recruitment Status: Completed
• First Posted: July 28, 2016
• Last Update Posted: August 28, 2020
• Sponsor: University of Illinois at Chicago
• Information provided by (Responsible Party): Richard B van Breemen, University of Illinois at Chicago

Study Description

Brief Summary:

Human safety studies were carried out to test whether hop 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 hop dietary supplement (previously tested in women at the University of Illinois at Chicago without any harmful effects) was given with four selected FDA-approved drugs to determine if the hop supplement can increase or decrease how these medications are absorbed, metabolized and excreted by the human body. Preclinical studies had predicted that the hop supplement might affect the metabolism or break down of these probe drugs.

Condition or disease	Intervention/treatment	Phase
Food-Drug Interactions	Dietary Supplement: Humulus lupulus	Not Applicable

Detailed Description:

At the start of a study, subjects were administered low doses of a mixture of four FDA-approved drugs (caffeine, tolbutamide, dextromethorphan, and alprazolam), and serial blood samples were drawn and analyzed for the concentration of each drug over time. Afterwards, participants consumed the hop dietary supplement twice daily for 14 days to allow for potential inhibition or induction of drug metabolizing enzymes and transporters. Thereafter, the same drugs were taken again to obtain a second measure of drug concentrations in blood over time. Changes in the concentration-time curve values for each probe drug obtained before and after ingestion of the supplement would indicate that metabolism of the probe drugs is impacted by the hop dietary supplement.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Hop Botanical Dietary Supplements - Metabolism and Safety in Women
• Actual Study Start Date: August 15, 2016
• Actual Primary Completion Date: September 10, 2018
• Actual Study Completion Date: September 24, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Humulus lupulus; Spent hop extract; 2 gelatin capsules (59.5 mg extract) per day for 14 days	Dietary Supplement: Humulus lupulus; Extract of spent hops standardized to xanthohumol, isoxanthohumol, 6-prenylnaringenin, and 8-prenylnaringenin; Other Name: hops

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve (AUC) [ Time Frame: baseline and 14 days ]
   Concentration of probe drugs from blood draws during the 14-day intervention were used to calculate area under the (extrapolated) concentration-time curve to determine any changes compared to pre-intervention.

Secondary Outcome Measures :

1. Apparent Clearance [ Time Frame: baseline and 14 days ]
   Concentration of probe drugs from blood draws during the 14-day intervention were used to calculate area under the (extrapolated) concentration-time curve to determine any changes compared to pre-intervention.
2. Peak Concentration [ Time Frame: baseline and 14 days ]
   Concentration of probe drugs from blood draws during the 14-day intervention were used to calculate peak concentration of probe drug to determine any changes compared to pre-intervention.
3. Time for Peak Concentration [ Time Frame: baseline and 14 days ]
   Concentration of probe drugs from blood draws during the 14-day intervention were used to calculate time for peak concentration of probe drug to determine any changes compared to pre-intervention.
4. Drug Half-life [ Time Frame: baseline and 14 days ]
   Concentration of probe drugs from blood draws during the 14-day intervention were used to calculate half-life of probe drug to determine any changes compared to pre-intervention.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• known allergies or hypersensitivity to caffeine, dextromethorphan, sulfonylureas (tolbutamide), benzodiazepines, red clover, licorice, or hops
• 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
• use of 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
• hops intake (whether as a botanical dietary supplement or beer) 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
• obesity (defined as >33 BMI)
• alcohol or drug abuse
• chronic diseases such as inflammatory bowel disease or diabetes

Contacts and Locations

Locations

United States, Illinois

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

Sponsors and Collaborators

University of Illinois at Chicago

Investigators

• Principal Investigator: Richard B van Breemen, Ph.D.; University of Illinois at Chicago

More Information

Additional Information:

University of Illinois at Chicago / National Institutes of Health Center for Botanical Dietary Supplements 

Publications of Results:

van Breemen RB, Chen L, Tonsing-Carter A, Banuvar S, Barengolts E, Viana M, Chen SN, Pauli GF, Bolton JL. Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women. J Agric Food Chem. 2020 May 6;68(18):5212-5220. doi: 10.1021/acs.jafc.0c01077. Epub 2020 Apr 24.

Other Publications:

van Breemen RB, Yuan Y, Banuvar S, Shulman LP, Qiu X, Alvarenga RF, Chen SN, Dietz BM, Bolton JL, Pauli GF, Krause E, Viana M, Nikolic D. Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops. Mol Nutr Food Res. 2014 Oct;58(10):1962-9. doi: 10.1002/mnfr.201400245. Epub 2014 Sep 16.

• Responsible Party: Richard B van Breemen, Principal Investigator, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT02848430
• Other Study ID Numbers: 2015-0651
• First Posted: July 28, 2016
• Last Update Posted: August 28, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Richard B van Breemen, University of Illinois at Chicago:

Humulus lupulus