Clinical trial NCT03140397: Oral Bioavailability and Bioactivity of Prenylflavonoids From Hops
Official title: Examination of the Bioavailability and Bioactivity of the Two Natural Food Ingredients 6-Prenylnaringenin and 8-Prenylnaringenin.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Safety After Oral Intake
Pharmacokinetics After Oral Intake
Immune Cells Activity
Keywords: Bioavailability
Pharmacokinetics
8-prenylnaringenin
6-prenylnaringenin
Prenylflavonoids
PBMC
Lead sponsor: University of Hohenheim
Sponsor class: OTHER
Collaborators: name: Universität Tübingen
First posted: 2017-05-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The prenylflavonoids 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN) are secondary plant substances, almost exclusively found in hops (Humulus lupulus). Both compounds have known potential biological properties, but poor bioavailability due to their low oral absorption and retention. Our study followed a single dose (500 mg 6- or 8-PN), placebo controlled, randomized, double-blind, three armed crossover study design with ≥2-week washout periods. Plasma, PBMC and urine samples were collected at intervals up to 24 h after intake. Investigators investigated the safety, pharmacokinetics and impact of oral prenylflavonoids on the function of cells of the immune system.


Eligibility criteria: Inclusion Criteria:

* Healthy Volunteers with blood chemistry values within normal ranges
* Age: 18-45 years
* BMI: 19-25 kg/m2

Exclusion Criteria:

* Pregnancy or lactation
* Alcohol and/or drug abuse
* Use of dietary supplements or any medications, except contraceptives
* Any known malignant, metabolic and endocrine diseases
* Previous cardiac infarction
* Dementia
* Participation in a clinical trial within the past 6 weeks prior to recruitment
* Physical activity of more than 5 h/wk

Primary outcomes:
measure: Mean area under the curve (AUC) of plasma concentration vs. time of total 6-prenylnaringenin [nmol/L*h]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
measure: Mean area under the curve (AUC) of plasma concentration vs. time of total 8-prenylnaringenin [nmol/L*h]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
measure: Mean maximum plasma concentration (Cmax) of total 6-prenylnaringenin [nmol/L]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
measure: Mean maximum plasma concentration (Cmax) of total 8-prenylnaringenin [nmol/L]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
measure: Time to reach maximum plasma concentration (Tmax) of total 6-prenylnaringenin [h]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
measure: Time to reach maximum plasma concentration (Tmax) of total 8-prenylnaringenin [h]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
measure: Cumulative urinary excretion of total 6-prenylnaringenin [nmol/g creatinine]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
measure: Cumulative urinary excretion of total 8-prenylnaringenin [nmol/g creatinine]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
measure: Cell count (dead cells/ml and living cells/ml) of PBMCs after 6-PN administration
timeFrame: 0, 6, and 24 h post dose
measure: Cell count (dead cells/ml and living cells/ml) of PBMCs after 8-PN administration
timeFrame: 0, 6, and 24 h post dose
measure: Cell viability of PBMCs after 6-PN administration
timeFrame: 0, 6, and 24 h post dose
measure: Cell viability of PBMCs after 8-PN administration
timeFrame: 0, 6, and 24 h post dose
Secondary outcomes:
measure: Serum aspartate transaminase activity [U/L]
timeFrame: 0, 4, 24h post-dose
measure: Serum alanine transaminase activity [U/L]
timeFrame: 0, 4, 24h post-dose
measure: Serum gamma-glutamyl transferase activity [U/L]
timeFrame: 0, 4, 24h post-dose
measure: Serum alkaline phosphatase activity [U/L]
timeFrame: 0, 4, 24h post-dose
measure: Serum bilirubin
timeFrame: 0, 4, 24h post-dose
measure: Serum uric acid [mg/dL]
timeFrame: 0, 4, 24h post-dose
measure: Serum creatinine [mg/dL]
timeFrame: 0, 4, 24h post-dose
measure: Serum total cholesterol [mg/dL]
timeFrame: 0, 4, 24h post-dose
measure: Serum HDL cholesterol [mg/dL]
timeFrame: 0, 4, 24h post-dose
measure: Serum LDL cholesterol [mg/dL]
timeFrame: 0, 4, 24h post-dose
measure: Serum triacylglycerols [mg/dL]
timeFrame: 0, 4, 24h post-dose
measure: LDL/HDL cholesterol ratio
timeFrame: 0, 4, 24h post-dose
measure: Serum cystatin C [mg/mL]
timeFrame: 0, 4, 24h post-dose
measure: Glomerular filtration rate [mL/min]
timeFrame: 0, 4, 24h post-dose
measure: Serum glucose [mg/dL]
timeFrame: 0, 24h post-dose
measure: Hemoglobin [g/dL]
timeFrame: 0, 24h post-dose
measure: Mean corpuscular hemoglobin concentration [g/dL]
timeFrame: 0, 24h post-dose
measure: Mean corpuscular hemoglobin [pg]
timeFrame: 0, 24h post-dose
measure: Mean corpuscular volume [fL]
timeFrame: 0, 24h post-dose
measure: Hematocrit [%]
timeFrame: 0, 24h post-dose
measure: Erythrocytes [/pL]
timeFrame: 0, 24h post-dose
measure: Thrombocytes [/nL]
timeFrame: 0, 24h post-dose
measure: Leucocytes [/nL]
timeFrame: 0, 24h post-dose
measure: Segmented granulocytes [%]
timeFrame: 0, 24h post-dose
measure: Lymphocytes [%]
timeFrame: 0, 24h post-dose
measure: Monocytes [%]
timeFrame: 0, 24h post-dose
measure: Basophil granulocytes [%]
timeFrame: 0, 24h post-dose
measure: Eosinophil granulocytes [%]
timeFrame: 0, 24h post-dose
Other outcomes:
Locations:
city: Stuttgart
country: Germany
facility: University of Hohenheim
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: Eberhard Karls University Tuebingen
state: Baden-Württemberg
Study officials:
affiliation: University of Hohenheim
name: Jan Frank, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Eberhard Karls University Tuebingen
name: Sascha Venturelli, Dr. med. Dr. rer. nat.
role: PRINCIPAL_INVESTIGATOR
affiliation: Eberhard Karls University Tuebingen
name: Christian Busch, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Calvo-Castro LA, Burkard M, Sus N, Scheubeck G, Leischner C, Lauer UM, Bosy-Westphal A, Hund V, Busch C, Venturelli S, Frank J. The Oral Bioavailability of 8-Prenylnaringenin from Hops (Humulus Lupulus L.) in Healthy Women and Men is Significantly Higher than that of its Positional Isomer 6-Prenylnaringenin in a Randomized Crossover Trial. Mol Nutr Food Res. 2018 Apr;62(7):e1700838. doi: 10.1002/mnfr.201700838. Epub 2018 Mar 1.