Clinical trial NCT03205787: Red Clover Botanical Dietary Supplements - Metabolism and Safety in Women
Official title: Red Clover Botanical Dietary Supplements - Metabolism and Safety in Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Food-drug Interaction
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 20
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Human safety studies were 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) was given with four selected FDA-approved drugs to determine if the red clover supplement can increase or decrease how these medications are absorbed, metabolized and excreted by the human body. Preclinical studies predicted that the red clover 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 took the red clover dietary supplement twice orally 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 were evaluated to determine if metabolism of the probe drugs was impacted by the red clover dietary supplement.

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, or red clover
* 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
* red clover or soy intake (whether as a botanical dietary supplement, 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
* chronic diseases such as diabetes.

Primary outcomes:
measure: Area Under the Curve (AUC)
timeFrame: baseline and 14 days
Secondary outcomes:
measure: Apparent Clearance
timeFrame: baseline and 14 days
measure: Peak Concentration
timeFrame: baseline and 14 days
measure: Time for Peak Concentration
timeFrame: baseline and 14 days
measure: Drug Half-life
timeFrame: baseline and 14 days
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Richard vanBreemen, PhD
role: STUDY_DIRECTOR
References:
citation: Muchiri RN, van Breemen RB. Single-Laboratory Validation of UHPLC-MS/MS Assays for Red Clover Isoflavones in Human Serum and Dietary Supplements. J AOAC Int. 2020 Jul 1;103(4):1160-1166. doi: 10.1093/jaoacint/qsaa033.