Increasing the Oral Bioavailability of 6-prenylnaringenin by Micellar Solubilization

Study Overview
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Brief Summary
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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.

Official Title
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Increasing the Oral Bioavailability of 6-prenylnaringenin by Micellar Solubilization

Conditions
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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
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* Dietary Supplement: Placebo
* Dietary Supplement: Native 6-prenylnaringenin
* Dietary Supplement: Micellar 6-prenylnaringenin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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6-prenylnaringenin, Bioavailability, Pharmacokinetics, PBMC