Increasing the Oral Bioavailability of 6-prenylnaringenin by Micellar Solubilization

Micellar encapsulation will be tested to increase the oral bioavailability in humans of 6-prenylnaringenin (6-PN) from hops (Humulus lupulus). The study follows a single dose (250 mg 6-PN), placebo controlled, randomized, double-blind, three armed crossover study design with ≥2-week washout periods. Plasma, urine and PBMC samples will be collected at intervals up to 24 h after intake of the native compound, the micellar formulation or placebo. The safety, pharmacokinetics and impact of oral prenylflavonoids on PBMC survival will be investigated.

Study Overview

• Status: Completed
• Conditions: Safety of Native vs. Micellar 6-PN After Oral Intake; Pharmacokinetics of Native vs. Micellar 6-PN After Oral Intake; PBMC Activity After Native vs. Micellar 6-PN Oral Intake
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Native 6-prenylnaringenin; Dietary supplement: Micellar 6-prenylnaringenin

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Stuttgart, Baden-Württemberg, Germany, 70599
      • University of Hohenheim
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Eberhard Karls University Tuebingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Mannitol and silicon dioxide	Dietary supplement: Placebo; Mannitol and silicon dioxide capsules
Experimental: Native 6-prenylnaringenin; 250 mg native 6-PN plus mannitol and silicon dioxide	Dietary supplement: Native 6-prenylnaringenin; 250 mg native 6-PN plus mannitol and silicon dioxide capsules
Experimental: Micellar 6-prenylnaringenin; 250 mg 6-PN in a micellar formulation with Tween-80 as adjuvant	Dietary supplement: Micellar 6-prenylnaringenin; 250 mg 6-PN in a micellar formulation with Tween-80 as adjuvant capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean area under the curve (AUC) of plasma concentration vs. time of total 6-PN [nmol/L*h]	Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase	0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose
Mean maximum plasma concentration (Cmax) of total 6-PN [nmol/L]	Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase	0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose
Time to reach maximum plasma concentration (Tmax) of total 6-PN [h]	Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase	0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose
Cumulative urinary excretion of total 6-PN [nmol/g creatinine]	Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase	0 h - 24 h post dose
Cell count (dead cells/ml and living cells/ml) of PBMCs after 6-PN administration		0 h, 6 h, and 24 h post dose
Cell viability of PBMCs after 6-PN administration		0 h, 6 h, and 24 h post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum aspartate transaminase activity [U/L]	0 h, 4 h, 24h post-dose
Serum alanine transaminase activity [U/L]	0 h, 4 h, 24h post-dose
Serum gamma-glutamyl transferase activity [U/L]	0 h, 4 h, 24h post-dose
Serum alkaline phosphatase activity [U/L]	0 h, 4 h, 24h post-dose
Serum bilirubin	0 h, 4 h, 24h post-dose
Serum uric acid [mg/dL]	0 h, 4 h, 24h post-dose
Serum creatinine [mg/dL]	0 h, 4 h, 24h post-dose
Serum total cholesterol [mg/dL]	0 h, 4 h, 24h post-dose
Serum HDL cholesterol [mg/dL]	0 h, 4 h, 24h post-dose
Serum LDL cholesterol [mg/dL]	0 h, 4 h, 24h post-dose
Serum triacylglycerols [mg/dL]	0 h, 4 h, 24h post-dose
LDL/HDL cholesterol ratio	0 h, 4 h, 24h post-dose
Glomerular filtration rate [mL/min]	0 h, 4 h, 24h post-dose
Serum glucose [mg/dL]	0 h, 4 h, 24h post-dose
Hemoglobin [g/dL]	0 h, 24 h post-dose
Mean corpuscular hemoglobin concentration [g/dL]	0 h, 24 h post-dose
Mean corpuscular hemoglobin [pg]	0 h, 24 h post-dose
Mean corpuscular volume [fL]	0 h, 24 h post-dose
Hematocrit [%]	0 h, 24 h post-dose
Erythrocytes [/pL]	0 h, 24 h post-dose
Thrombocytes [/nL]	0 h, 24 h post-dose
Leucocytes [/nL]	0 h, 24 h post-dose

Collaborators and Investigators

• Sponsor: University of Hohenheim
• Collaborators: Universität Tübingen
• Investigators: Principal Investigator: Jan Frank, Prof. Dr., University of Hohenheim; Principal Investigator: Sascha Venturelli, Dr. med. Dr. rer. nat., University Hospital, Eberhard Karls University Tuebingen, Germany; Principal Investigator: Christian Busch, Dr. med., University Hospital, Eberhard Karls University Tuebingen, Germany

Publications and helpful links

Helpful Links

• Website of the research group

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2017
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: September 14, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 18, 2017

Study Record Updates

• Last Update Posted (Actual): October 10, 2018
• Last Update Submitted That Met QC Criteria: October 9, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Bioavailability; PBMC; 6-prenylnaringenin
• Other Study ID Numbers: HS-PF2-2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No