<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/NCT04421716</url>
  </required_header>
  <id_info>
    <org_study_id>HSC20190940H</org_study_id>
    <nct_id>NCT04421716</nct_id>
  </id_info>
  <brief_title>Testing the Bioavailability of Phytonutrients, Curcumin and Ursolic Acid</brief_title>
  <official_title>Phase I Clinical Trial Testing the Bioavailability of Phytonutrients, Curcumin and Ursolic Acid</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center at San Antonio</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Texas Health Science Center at San Antonio</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this research is to investigate the bioavailability of curcumin&#xD;
      (CURC) and ursolic acid (UA) in a phase I clinical trial in healthy men and obtain biological&#xD;
      material for bioavailability analysis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Once a subject is consented and assigned to a cohort, the subject may undergo a digital&#xD;
      rectal exam (DRE) and rectal swab fecal collection and provide research blood (including CBC&#xD;
      and CMP safety labs) and urine. Medical history data will be collected and reviewed. The PI&#xD;
      and/or study staff will provide supplement administration and supplement diary education&#xD;
      prior to the subject starting their dose of UA, CURC, or UA and CURC combination.&#xD;
      Pharmacokinetic (PK) and pharmacodynamic (PD) assessments will be collected at pre-dose and 6&#xD;
      and 24 hours after the first dose. Urine will also be collected at pre dose and 24 hours post&#xD;
      dose. The dosing period will be for a total of 2 weeks (± 3 days). On the last day of dosing,&#xD;
      subjects will attend a research only visit at which the subject may undergo a digital rectal&#xD;
      exam (DRE) and rectal swab fecal collection and provide research blood and urine. At this&#xD;
      time, the subject's supplement diary will be reviewed and a safety/AE assessment will be&#xD;
      completed. In addition, research CBC and CMP safety labs will be collected. If a subject&#xD;
      initially enrolled in Cohort 1 or 2 decides to continue in Cohort 3, the subject will undergo&#xD;
      a wash out period of at least 4 weeks and repeat all study procedures for Cohort 3.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 20, 2020</start_date>
  <completion_date type="Actual">April 16, 2021</completion_date>
  <primary_completion_date type="Actual">November 30, 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Cohort 1 and 2 will receive either UA or CURC and Cohort 3 will receive a combination of UA and CURC. Subjects initially enrolled in Cohorts 1 and 2 may have the option to continue in Cohort 3.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number, frequency, duration, and relation of toxicity events</measure>
    <time_frame>Baseline to 2 weeks</time_frame>
    <description>Safety will be compared to evaluate the number, frequency, duration, and relation of toxicity events to CURC and UA, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak serum concentration</measure>
    <time_frame>Baseline to 2 weeks</time_frame>
    <description>Dose response curve representing the pharmacokinetic parameter peak serum concentration (Cmax) of ursolic acid, curcumin, and their metabolites will be graphed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to reach peak serum concentration</measure>
    <time_frame>Baseline to 2 weeks</time_frame>
    <description>The pharmacokinetic parameter, the area under the curve (Tmax) representing the time it takes to reach Cmax of ursolic acid, curcumin, and their metabolites will be graphed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Half-life</measure>
    <time_frame>Baseline to 2 weeks</time_frame>
    <description>The pharmacokinetic parameter, half-life of ursolic acid, curcumin, and their metabolites will be graphed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Microbiome Alpha Diversity</measure>
    <time_frame>Baseline to 2 weeks</time_frame>
    <description>Number of bacteria collected from rectal culture sample will be assessed before and after each exposure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiome Beta Diversity</measure>
    <time_frame>Baseline to 2 weeks</time_frame>
    <description>Proportions of bacteria collected from rectal culture sample will be assessed before and after each exposure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolite Panels</measure>
    <time_frame>Baseline to 2 weeks</time_frame>
    <description>Metabolite panels will be placed into quartiles and compared to predicted function from the bioinformatics tool Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Bioavailability of Phytonutrients</condition>
  <arm_group>
    <arm_group_label>Ursolic Acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of Ursolic Acid twice a day for 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Curcumin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of Curcumin twice a day for 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ursolic Acid and Curcumin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of Ursolic Acid and Curcumin. If subjects from Cohort 1 or 2 wish to continue in the study, they will undergo a washout period of at least 4 weeks before participating in Cohort 3</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ursolic Acid</intervention_name>
    <description>Ursolic Acid 150mg</description>
    <arm_group_label>Ursolic Acid</arm_group_label>
    <arm_group_label>Ursolic Acid and Curcumin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Curcumin</intervention_name>
    <description>Curcumin 600mg</description>
    <arm_group_label>Curcumin</arm_group_label>
    <arm_group_label>Ursolic Acid and Curcumin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be able to give informed consent&#xD;
&#xD;
          -  Be men age 18 or older&#xD;
&#xD;
          -  Able to stop supplements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to give informed consent&#xD;
&#xD;
          -  Age &lt; 18&#xD;
&#xD;
          -  Woman&#xD;
&#xD;
          -  Prisoners&#xD;
&#xD;
          -  Diagnosed cancer&#xD;
&#xD;
          -  Unable to swallow pills&#xD;
&#xD;
          -  Unable to stop supplements&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael A Liss, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Health at San Antonio</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>May 4, 2021</last_update_submitted>
  <last_update_submitted_qc>May 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ursolic acid</mesh_term>
    <mesh_term>Curcumin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data will be available upon request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>De-identified data will be available upon request following study completion for approx. 1 year.</ipd_time_frame>
    <ipd_access_criteria>Access available upon request.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT04421716
org study id: HSC20190940H
nct id: NCT04421716
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this research is to investigate the bioavailability of curcumin
      (CURC) and ursolic acid (UA) in a phase I clinical trial in healthy men and obtain biological
      material for bioavailability analysis.
Once a subject is consented and assigned to a cohort, the subject may undergo a digital
      rectal exam (DRE) and rectal swab fecal collection and provide research blood (including CBC
      and CMP safety labs) and urine. Medical history data will be collected and reviewed. The PI
      and/or study staff will provide supplement administration and supplement diary education
      prior to the subject starting their dose of UA, CURC, or UA and CURC combination.
      Pharmacokinetic (PK) and pharmacodynamic (PD) assessments will be collected at pre-dose and 6
      and 24 hours after the first dose. Urine will also be collected at pre dose and 24 hours post
      dose. The dosing period will be for a total of 2 weeks (± 3 days). On the last day of dosing,
      subjects will attend a research only visit at which the subject may undergo a digital rectal
      exam (DRE) and rectal swab fecal collection and provide research blood and urine. At this
      time, the subject's supplement diary will be reviewed and a safety/AE assessment will be
      completed. In addition, research CBC and CMP safety labs will be collected. If a subject
      initially enrolled in Cohort 1 or 2 decides to continue in Cohort 3, the subject will undergo
      a wash out period of at least 4 weeks and repeat all study procedures for Cohort 3.
allocation: Non-Randomized
intervention model: Crossover Assignment
intervention model description: Cohort 1 and 2 will receive either UA or CURC and Cohort 3 will receive a combination of UA and CURC. Subjects initially enrolled in Cohorts 1 and 2 may have the option to continue in Cohort 3.
primary purpose: Basic Science
masking: None (Open Label)
measure: Number, frequency, duration, and relation of toxicity events
time frame: Baseline to 2 weeks
description: Safety will be compared to evaluate the number, frequency, duration, and relation of toxicity events to CURC and UA, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03.
measure: Peak serum concentration
time frame: Baseline to 2 weeks
description: Dose response curve representing the pharmacokinetic parameter peak serum concentration (Cmax) of ursolic acid, curcumin, and their metabolites will be graphed.
measure: Time to reach peak serum concentration
time frame: Baseline to 2 weeks
description: The pharmacokinetic parameter, the area under the curve (Tmax) representing the time it takes to reach Cmax of ursolic acid, curcumin, and their metabolites will be graphed.
measure: Half-life
time frame: Baseline to 2 weeks
description: The pharmacokinetic parameter, half-life of ursolic acid, curcumin, and their metabolites will be graphed.
measure: Microbiome Alpha Diversity
time frame: Baseline to 2 weeks
description: Number of bacteria collected from rectal culture sample will be assessed before and after each exposure
measure: Microbiome Beta Diversity
time frame: Baseline to 2 weeks
description: Proportions of bacteria collected from rectal culture sample will be assessed before and after each exposure
measure: Metabolite Panels
time frame: Baseline to 2 weeks
description: Metabolite panels will be placed into quartiles and compared to predicted function from the bioinformatics tool Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software.
arm group label: Ursolic Acid
arm group type: Experimental
description: Administration of Ursolic Acid twice a day for 2 weeks
arm group label: Curcumin
arm group type: Experimental
description: Administration of Curcumin twice a day for 2 weeks
arm group label: Ursolic Acid and Curcumin
arm group type: Experimental
description: Administration of Ursolic Acid and Curcumin. If subjects from Cohort 1 or 2 wish to continue in the study, they will undergo a washout period of at least 4 weeks before participating in Cohort 3
intervention type: Drug
intervention name: Ursolic Acid
description: Ursolic Acid 150mg
arm group label: Ursolic Acid
arm group label: Ursolic Acid and Curcumin
intervention type: Drug
intervention name: Curcumin
description: Curcumin 600mg
arm group label: Curcumin
arm group label: Ursolic Acid and Curcumin
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Michael A Liss, MD
role: Principal Investigator
affiliation: University of Texas Health at San Antonio
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ursolic acid
mesh term: Curcumin
sharing ipd: Yes
ipd description: De-identified individual participant data will be available upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: De-identified data will be available upon request following study completion for approx. 1 year.
ipd access criteria: Access available upon request.