NCT03140397

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at P25-P50 for early_phase_1

Timeline
Completed

Started Jan 2016

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2016

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

May 2, 2017

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 4, 2017

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2017

Completed
Last Updated

March 30, 2018

Status Verified

March 1, 2018

Enrollment Period

1.2 years

First QC Date

May 2, 2017

Last Update Submit

March 29, 2018

Conditions

Safety After Oral IntakePharmacokinetics After Oral IntakeImmune Cells Activity

Keywords

BioavailabilityPharmacokinetics8-prenylnaringenin6-prenylnaringeninPrenylflavonoidsPBMC

Outcome Measures

Primary Outcomes (12)

  • Mean area under the curve (AUC) of plasma concentration vs. time of total 6-prenylnaringenin [nmol/L*h]

    Total 6-PN after deconjugation with beta-glucuronidase/sulphatase

    0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose

  • Mean area under the curve (AUC) of plasma concentration vs. time of total 8-prenylnaringenin [nmol/L*h]

    Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase

    0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose

  • Mean maximum plasma concentration (Cmax) of total 6-prenylnaringenin [nmol/L]

    Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase

    0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose

  • Mean maximum plasma concentration (Cmax) of total 8-prenylnaringenin [nmol/L]

    Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase

    0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose

  • Time to reach maximum plasma concentration (Tmax) of total 6-prenylnaringenin [h]

    Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase

    0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose

  • Time to reach maximum plasma concentration (Tmax) of total 8-prenylnaringenin [h]

    Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase

    0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose

  • Cumulative urinary excretion of total 6-prenylnaringenin [nmol/g creatinine]

    Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase

    0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose

  • Cumulative urinary excretion of total 8-prenylnaringenin [nmol/g creatinine]

    Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase

    0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose

  • Cell count (dead cells/ml and living cells/ml) of PBMCs after 6-PN administration

    0, 6, and 24 h post dose

  • Cell count (dead cells/ml and living cells/ml) of PBMCs after 8-PN administration

    0, 6, and 24 h post dose

  • Cell viability of PBMCs after 6-PN administration

    0, 6, and 24 h post dose

  • Cell viability of PBMCs after 8-PN administration

    0, 6, and 24 h post dose

Secondary Outcomes (28)

  • Serum aspartate transaminase activity [U/L]

    0, 4, 24h post-dose

  • Serum alanine transaminase activity [U/L]

    0, 4, 24h post-dose

  • Serum gamma-glutamyl transferase activity [U/L]

    0, 4, 24h post-dose

  • Serum alkaline phosphatase activity [U/L]

    0, 4, 24h post-dose

  • Serum bilirubin

    0, 4, 24h post-dose

  • +23 more secondary outcomes

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Capsules filled with mannitol and silicon dioxide

Dietary Supplement: Placebo

6-prenylnaringenin

EXPERIMENTAL

500 mg 6-PN plus mannitol and silicon dioxide

Dietary Supplement: 6-prenylnaringenin

8-prenylnaringenin

EXPERIMENTAL

500 mg 8-PN plus mannitol and silicon dioxide

Dietary Supplement: 8-prenylnaringenin

Interventions

PlaceboDIETARY_SUPPLEMENT
Placebo
6-prenylnaringeninDIETARY_SUPPLEMENT
Also known as: 6-PN
6-prenylnaringenin
8-prenylnaringeninDIETARY_SUPPLEMENT
Also known as: 8-PN
8-prenylnaringenin

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of Hohenheim

Stuttgart, Baden-Wurttemberg, 70599, Germany

Location

Eberhard Karls University Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Related Publications (1)

  • 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.

    PMID: 29363261DERIVED

Related Links

MeSH Terms

Interventions

6-prenylnaringenin8-prenylnaringenin

Study Officials

  • Jan Frank, Prof. Dr.

    University of Hohenheim

    PRINCIPAL INVESTIGATOR

  • Sascha Venturelli, Dr. med. Dr. rer. nat.

    Eberhard Karls University Tuebingen

    PRINCIPAL INVESTIGATOR

  • Christian Busch, Dr. med.

    Eberhard Karls University Tuebingen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 2, 2017

First Posted

May 4, 2017

Study Start

January 1, 2016

Primary Completion

April 1, 2017

Study Completion

December 31, 2017

Last Updated

March 30, 2018

Record last verified: 2018-03

Data Sharing

IPD Sharing
Will not share

Locations

DE(2)