<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03286777</url>
  </required_header>
  <id_info>
    <org_study_id>HS-PF2-2017</org_study_id>
    <nct_id>NCT03286777</nct_id>
  </id_info>
  <brief_title>Increasing the Oral Bioavailability of 6-prenylnaringenin by Micellar Solubilization</brief_title>
  <official_title>Increasing the Oral Bioavailability of 6-prenylnaringenin by Micellar Solubilization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Hohenheim</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universität Tübingen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Hohenheim</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Micellar encapsulation will be tested to increase the oral bioavailability in humans of&#xD;
      6-prenylnaringenin (6-PN) from hops (Humulus lupulus). The study follows a single dose (250&#xD;
      mg 6-PN), placebo controlled, randomized, double-blind, three armed crossover study design&#xD;
      with ≥2-week washout periods. Plasma, urine and PBMC samples will be collected at intervals&#xD;
      up to 24 h after intake of the native compound, the micellar formulation or placebo. The&#xD;
      safety, pharmacokinetics and impact of oral prenylflavonoids on PBMC survival will be&#xD;
      investigated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 22, 2017</start_date>
  <completion_date type="Actual">July 1, 2018</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean area under the curve (AUC) of plasma concentration vs. time of total 6-PN [nmol/L*h]</measure>
    <time_frame>0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose</time_frame>
    <description>Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean maximum plasma concentration (Cmax) of total 6-PN [nmol/L]</measure>
    <time_frame>0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose</time_frame>
    <description>Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to reach maximum plasma concentration (Tmax) of total 6-PN [h]</measure>
    <time_frame>0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose</time_frame>
    <description>Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative urinary excretion of total 6-PN [nmol/g creatinine]</measure>
    <time_frame>0 h - 24 h post dose</time_frame>
    <description>Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cell count (dead cells/ml and living cells/ml) of PBMCs after 6-PN administration</measure>
    <time_frame>0 h, 6 h, and 24 h post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cell viability of PBMCs after 6-PN administration</measure>
    <time_frame>0 h, 6 h, and 24 h post dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum aspartate transaminase activity [U/L]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum alanine transaminase activity [U/L]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum gamma-glutamyl transferase activity [U/L]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum alkaline phosphatase activity [U/L]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum bilirubin</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum uric acid [mg/dL]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum creatinine [mg/dL]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum total cholesterol [mg/dL]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum HDL cholesterol [mg/dL]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum LDL cholesterol [mg/dL]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum triacylglycerols [mg/dL]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LDL/HDL cholesterol ratio</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glomerular filtration rate [mL/min]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum glucose [mg/dL]</measure>
    <time_frame>0 h, 4 h, 24h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin [g/dL]</measure>
    <time_frame>0 h, 24 h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean corpuscular hemoglobin concentration [g/dL]</measure>
    <time_frame>0 h, 24 h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean corpuscular hemoglobin [pg]</measure>
    <time_frame>0 h, 24 h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean corpuscular volume [fL]</measure>
    <time_frame>0 h, 24 h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematocrit [%]</measure>
    <time_frame>0 h, 24 h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythrocytes [/pL]</measure>
    <time_frame>0 h, 24 h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thrombocytes [/nL]</measure>
    <time_frame>0 h, 24 h post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leucocytes [/nL]</measure>
    <time_frame>0 h, 24 h post-dose</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Safety of Native vs. Micellar 6-PN After Oral Intake</condition>
  <condition>Pharmacokinetics of Native vs. Micellar 6-PN After Oral Intake</condition>
  <condition>PBMC Activity After Native vs. Micellar 6-PN Oral Intake</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Mannitol and silicon dioxide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Native 6-prenylnaringenin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>250 mg native 6-PN plus mannitol and silicon dioxide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Micellar 6-prenylnaringenin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>250 mg 6-PN in a micellar formulation with Tween-80 as adjuvant</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Mannitol and silicon dioxide capsules</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Native 6-prenylnaringenin</intervention_name>
    <description>250 mg native 6-PN plus mannitol and silicon dioxide capsules</description>
    <arm_group_label>Native 6-prenylnaringenin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Micellar 6-prenylnaringenin</intervention_name>
    <description>250 mg 6-PN in a micellar formulation with Tween-80 as adjuvant capsules</description>
    <arm_group_label>Micellar 6-prenylnaringenin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers with blood chemistry values within normal ranges&#xD;
&#xD;
          -  Age: 18-45 years&#xD;
&#xD;
          -  BMI: 19-25 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Alcohol and/or drug abuse&#xD;
&#xD;
          -  Use of dietary supplements or any medications, except contraceptives&#xD;
&#xD;
          -  Any known malignant, metabolic and endocrine diseases&#xD;
&#xD;
          -  Previous cardiac infarction&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  Participation in a clinical trial within the past 6 weeks prior to recruitment&#xD;
&#xD;
          -  Physical activity of more than 5 h/wk&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jan Frank, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Hohenheim</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sascha Venturelli, Dr. med. Dr. rer. nat.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Eberhard Karls University Tuebingen, Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christian Busch, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Eberhard Karls University Tuebingen, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Hohenheim</name>
      <address>
        <city>Stuttgart</city>
        <state>Baden-Württemberg</state>
        <zip>70599</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eberhard Karls University Tuebingen</name>
      <address>
        <city>Tübingen</city>
        <state>Baden-Württemberg</state>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.nutrition-research.de/</url>
    <description>Website of the research group</description>
  </link>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>October 9, 2018</last_update_submitted>
  <last_update_submitted_qc>October 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>6-prenylnaringenin</keyword>
  <keyword>Bioavailability</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>PBMC</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03286777
org study id: HS-PF2-2017
nct id: NCT03286777
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Mean area under the curve (AUC) of plasma concentration vs. time of total 6-PN [nmol/L*h]
time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose
description: Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase
measure: Mean maximum plasma concentration (Cmax) of total 6-PN [nmol/L]
time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose
description: Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase
measure: Time to reach maximum plasma concentration (Tmax) of total 6-PN [h]
time frame: 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h post dose
description: Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase
measure: Cumulative urinary excretion of total 6-PN [nmol/g creatinine]
time frame: 0 h - 24 h post dose
description: Total 6-PN determined after deconjugation with beta-glucuronidase/sulphatase
measure: Cell count (dead cells/ml and living cells/ml) of PBMCs after 6-PN administration
time frame: 0 h, 6 h, and 24 h post dose
measure: Cell viability of PBMCs after 6-PN administration
time frame: 0 h, 6 h, and 24 h post dose
measure: Serum aspartate transaminase activity [U/L]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum alanine transaminase activity [U/L]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum gamma-glutamyl transferase activity [U/L]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum alkaline phosphatase activity [U/L]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum bilirubin
time frame: 0 h, 4 h, 24h post-dose
measure: Serum uric acid [mg/dL]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum creatinine [mg/dL]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum total cholesterol [mg/dL]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum HDL cholesterol [mg/dL]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum LDL cholesterol [mg/dL]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum triacylglycerols [mg/dL]
time frame: 0 h, 4 h, 24h post-dose
measure: LDL/HDL cholesterol ratio
time frame: 0 h, 4 h, 24h post-dose
measure: Glomerular filtration rate [mL/min]
time frame: 0 h, 4 h, 24h post-dose
measure: Serum glucose [mg/dL]
time frame: 0 h, 4 h, 24h post-dose
measure: Hemoglobin [g/dL]
time frame: 0 h, 24 h post-dose
measure: Mean corpuscular hemoglobin concentration [g/dL]
time frame: 0 h, 24 h post-dose
measure: Mean corpuscular hemoglobin [pg]
time frame: 0 h, 24 h post-dose
measure: Mean corpuscular volume [fL]
time frame: 0 h, 24 h post-dose
measure: Hematocrit [%]
time frame: 0 h, 24 h post-dose
measure: Erythrocytes [/pL]
time frame: 0 h, 24 h post-dose
measure: Thrombocytes [/nL]
time frame: 0 h, 24 h post-dose
measure: Leucocytes [/nL]
time frame: 0 h, 24 h post-dose
arm group label: Placebo
arm group type: Placebo Comparator
description: Mannitol and silicon dioxide
arm group label: Native 6-prenylnaringenin
arm group type: Experimental
description: 250 mg native 6-PN plus mannitol and silicon dioxide
arm group label: Micellar 6-prenylnaringenin
arm group type: Experimental
description: 250 mg 6-PN in a micellar formulation with Tween-80 as adjuvant
intervention type: Dietary Supplement
intervention name: Placebo
description: Mannitol and silicon dioxide capsules
arm group label: Placebo
intervention type: Dietary Supplement
intervention name: Native 6-prenylnaringenin
description: 250 mg native 6-PN plus mannitol and silicon dioxide capsules
arm group label: Native 6-prenylnaringenin
intervention type: Dietary Supplement
intervention name: Micellar 6-prenylnaringenin
description: 250 mg 6-PN in a micellar formulation with Tween-80 as adjuvant capsules
arm group label: Micellar 6-prenylnaringenin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jan Frank, Prof. Dr.
role: Principal Investigator
affiliation: University of Hohenheim
last name: Sascha Venturelli, Dr. med. Dr. rer. nat.
role: Principal Investigator
affiliation: University Hospital, Eberhard Karls University Tuebingen, Germany
last name: Christian Busch, Dr. med.
role: Principal Investigator
affiliation: University Hospital, Eberhard Karls University Tuebingen, Germany
facility: 
facility: 
country: Germany
url: http://www.nutrition-research.de/
description: Website of the research group
responsible party type: Sponsor