Hop Botanical Dietary Supplements - Metabolism and Safety in Women

Study Overview
=================
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.

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.

Official Title
-----------------
Hop Botanical Dietary Supplements - Metabolism and Safety in Women

Conditions
-----------------
Food-Drug Interactions

Intervention / Treatment
-----------------
* Dietary Supplement: Humulus lupulus


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Humulus lupulus<br>Spent hop extract; 2 gelatin capsules (59.5 mg extract) per day for 14 days | Dietary Supplement: Humulus lupulus<br>* Extract of spent hops standardized to xanthohumol, isoxanthohumol, 6-prenylnaringenin, and 8-prenylnaringenin<br>* Other names: hops;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) | 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. | baseline and 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent Clearance | 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. | baseline and 14 days | 
| Peak Concentration | 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. | baseline and 14 days | 
| Time for Peak Concentration | 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. | baseline and 14 days | 
| Drug Half-life | 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. | baseline and 14 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Humulus lupulus