<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/NCT04464070</url>
  </required_header>
  <id_info>
    <org_study_id>150895</org_study_id>
    <nct_id>NCT04464070</nct_id>
  </id_info>
  <brief_title>Pathways of Eicosanoid Metabolism</brief_title>
  <official_title>Novel Pathways of Eicosanoid Metabolism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prostaglandins are important signaling compounds formed from arachidonic acid. The enzymes&#xD;
      that form prostaglandins, cyclooxygenase-1 and -2 are the targets of non-steroidal&#xD;
      anti-inflammatory drugs (NSAIDs). Because prostaglandins are very unstable in the body, they&#xD;
      can not be measured directly. Instead, their metabolites are isolated from urine or blood and&#xD;
      quantified as markers of formation of the parent, active compounds.&#xD;
&#xD;
      The investigators are testing the hypothesis that there is a previously unrecognized&#xD;
      metabolic pathway between two prostaglandins. The investigators hypothesize that&#xD;
      prostaglandin D2 (PGD2), in addition to its known metabolism to PGD-M, is also metabolized to&#xD;
      11-dehydro-thromboxane B2 (11-dehydro-TxB2).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this study is to determine whether PGD2 is metabolized to 11-dehydro-TxB2 in&#xD;
      humans. Because the levels of PGD2 and its metabolite, PGD-M, are low in human urine, the&#xD;
      investigators will use the model of niacin-induced flushing which is associated with a&#xD;
      increased release of PGD2 from skin cells. It has been demonstrated that increased formation&#xD;
      of PGD2 is associated with increased levels of urinary 11-dehydro-TxB2 in patients with&#xD;
      mastocytosis.&#xD;
&#xD;
      In order to test whether niacin-induced biosynthesis of PGD2 is associated with formation of&#xD;
      11-dehydro-TxB2 the investigators will measure prostaglandin metabolites in blood and urine&#xD;
      of volunteers receiving niacin. In addition, subjects will be treated with low or high dose&#xD;
      aspirin prior to niacin to analyze the contribution of cyclooxygenase enzymes to biosynthesis&#xD;
      of PGD2.&#xD;
&#xD;
      Arm 1: Subjects will receive 500 mg niacin. The subjects will collect urine (3-10 ml each)&#xD;
      before niacin and every one-two hours after niacin for 10 h. Subjects will have blood drawn&#xD;
      (2 teaspoons) before and at 0.5-1 h after niacin.&#xD;
&#xD;
      Arm 2: Subjects will take 81 mg aspirin (1 tablet of low-dose aspirin) daily for 7 days&#xD;
      before niacin. Urine collection will be before and after aspirin, before niacin, and then in&#xD;
      intervals as in arm 1. There will be a blood collection before niacin and 0.5-1 h after&#xD;
      niacin.&#xD;
&#xD;
      Arm 3: Subjects will take 325 mg aspirin (1 tablet of regular strength aspirin) daily for 7&#xD;
      days before niacin. Urine collection will be before and after aspirin, before niacin, and&#xD;
      then in intervals as in arm 1.&#xD;
&#xD;
      Arm 4: Subjects will be infused with 10 μg of deuterated PGD2 in a forearm vein over the&#xD;
      course of 30 min. Subjects will collect a urine sample before and every two hours after&#xD;
      deuterated PGD2 for 10 h.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">August 15, 2020</start_date>
  <completion_date type="Anticipated">August 4, 2024</completion_date>
  <primary_completion_date type="Actual">May 31, 2023</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Participants may be participating in all 4 arms of the study or in less than 4 arms.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>prostaglandin metabolites</measure>
    <time_frame>0-10 hours</time_frame>
    <description>metabolites will be quantified in urine and blood</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Metabolism of Prostaglandin D2</condition>
  <arm_group>
    <arm_group_label>niacin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Blood (10 ml) will be drawn from the subject. Immediately before or after the blood draw the subject will collect a urine (3-10 ml) sample. After the baseline blood draw and the urine sample is collected the subject will take 500 mg of niacin. The niacin will not be an extended release formulation. Subjects will be encouraged to drink plenty of water during the study. Subjects are instructed to collect urine 1, 2, 4, 6, 8, and 10 hours after niacin administration. Subjects will collect their urine in separate plastic tubes that will be provided to them.&#xD;
Approximately 1-2 h after niacin administration a second blood sample (10 ml) will be drawn from the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>niacin + low-dose aspirin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will provide a urine sample. They will receive 7 tablets of low-dose aspirin (81 mg) and be instructed to take one tablet daily for 7 days. On the seventh day, they return to have blood drawn, urine collected, and receive niacin as described in arm 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>niacin + regular-strength aspirin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will provide a urine sample. They will receive 7 tablets of regular-strength aspirin (325 mg) and be instructed to take one tablet daily for 7 days. On the seventh day, they return to have blood drawn, urine collected, and receive niacin as described in arm 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>deuterated PGD2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will come to the clinical research center. Volunteers will provide a urine sample. The volunteers will be fitted to record an electrocardiogram (ECG) and blood pressure. ECG will be recorded continuously. Blood pressure will be taken at baseline and every 10 minutes thereafter for one hour. The solution with deuterated PGD2 (10 microgram) will be infused over the course of 30 min. Volunteers will be monitored for 1 h after the end of the infusion, and volunteers will start collecting urine in intervals up to 10 h.&#xD;
Infusion of the deuterated PGD2 solution will be performed in the presence of a physician. The injection solution will be prepared by Vanderbilt University Medical Center (VUMC) Investigational Drug Services. The solution will be sterile and pyrogen free.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>niacin</intervention_name>
    <description>induce biosynthesis of PGD2</description>
    <arm_group_label>niacin</arm_group_label>
    <arm_group_label>niacin + low-dose aspirin</arm_group_label>
    <arm_group_label>niacin + regular-strength aspirin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>aspirin</intervention_name>
    <description>inhibition of cyclooxygenase</description>
    <arm_group_label>niacin + low-dose aspirin</arm_group_label>
    <arm_group_label>niacin + regular-strength aspirin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PGD2</intervention_name>
    <description>labeled precursor</description>
    <arm_group_label>deuterated PGD2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Normal, healthy volunteers not currently taking any medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of anti-inflammatory/over-the-counter pain medications (NSAIDs) up to 2 weeks&#xD;
             prior to study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claus M Schneider, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>Claus Schneider</investigator_full_name>
    <investigator_title>Associate Professor of Pharmacology</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Niacin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD (study protocol, informed consent forms) will be shared upon a justified request by an investigator.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>IPD will become available from the beginning of the study until completion.</ipd_time_frame>
    <ipd_access_criteria>Researchers need to make a justified 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/NCT04464070
org study id: 150895
nct id: NCT04464070
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Prostaglandins are important signaling compounds formed from arachidonic acid. The enzymes
      that form prostaglandins, cyclooxygenase-1 and -2 are the targets of non-steroidal
      anti-inflammatory drugs (NSAIDs). Because prostaglandins are very unstable in the body, they
      can not be measured directly. Instead, their metabolites are isolated from urine or blood and
      quantified as markers of formation of the parent, active compounds.

      The investigators are testing the hypothesis that there is a previously unrecognized
      metabolic pathway between two prostaglandins. The investigators hypothesize that
      prostaglandin D2 (PGD2), in addition to its known metabolism to PGD-M, is also metabolized to
      11-dehydro-thromboxane B2 (11-dehydro-TxB2).
The objective of this study is to determine whether PGD2 is metabolized to 11-dehydro-TxB2 in
      humans. Because the levels of PGD2 and its metabolite, PGD-M, are low in human urine, the
      investigators will use the model of niacin-induced flushing which is associated with a
      increased release of PGD2 from skin cells. It has been demonstrated that increased formation
      of PGD2 is associated with increased levels of urinary 11-dehydro-TxB2 in patients with
      mastocytosis.

      In order to test whether niacin-induced biosynthesis of PGD2 is associated with formation of
      11-dehydro-TxB2 the investigators will measure prostaglandin metabolites in blood and urine
      of volunteers receiving niacin. In addition, subjects will be treated with low or high dose
      aspirin prior to niacin to analyze the contribution of cyclooxygenase enzymes to biosynthesis
      of PGD2.

      Arm 1: Subjects will receive 500 mg niacin. The subjects will collect urine (3-10 ml each)
      before niacin and every one-two hours after niacin for 10 h. Subjects will have blood drawn
      (2 teaspoons) before and at 0.5-1 h after niacin.

      Arm 2: Subjects will take 81 mg aspirin (1 tablet of low-dose aspirin) daily for 7 days
      before niacin. Urine collection will be before and after aspirin, before niacin, and then in
      intervals as in arm 1. There will be a blood collection before niacin and 0.5-1 h after
      niacin.

      Arm 3: Subjects will take 325 mg aspirin (1 tablet of regular strength aspirin) daily for 7
      days before niacin. Urine collection will be before and after aspirin, before niacin, and
      then in intervals as in arm 1.

      Arm 4: Subjects will be infused with 10 μg of deuterated PGD2 in a forearm vein over the
      course of 30 min. Subjects will collect a urine sample before and every two hours after
      deuterated PGD2 for 10 h.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Participants may be participating in all 4 arms of the study or in less than 4 arms.
primary purpose: Basic Science
masking: None (Open Label)
measure: prostaglandin metabolites
time frame: 0-10 hours
description: metabolites will be quantified in urine and blood
arm group label: niacin
arm group type: Experimental
description: Blood (10 ml) will be drawn from the subject. Immediately before or after the blood draw the subject will collect a urine (3-10 ml) sample. After the baseline blood draw and the urine sample is collected the subject will take 500 mg of niacin. The niacin will not be an extended release formulation. Subjects will be encouraged to drink plenty of water during the study. Subjects are instructed to collect urine 1, 2, 4, 6, 8, and 10 hours after niacin administration. Subjects will collect their urine in separate plastic tubes that will be provided to them.
Approximately 1-2 h after niacin administration a second blood sample (10 ml) will be drawn from the subject.
arm group label: niacin + low-dose aspirin
arm group type: Experimental
description: Volunteers will provide a urine sample. They will receive 7 tablets of low-dose aspirin (81 mg) and be instructed to take one tablet daily for 7 days. On the seventh day, they return to have blood drawn, urine collected, and receive niacin as described in arm 1.
arm group label: niacin + regular-strength aspirin
arm group type: Experimental
description: Volunteers will provide a urine sample. They will receive 7 tablets of regular-strength aspirin (325 mg) and be instructed to take one tablet daily for 7 days. On the seventh day, they return to have blood drawn, urine collected, and receive niacin as described in arm 1.
arm group label: deuterated PGD2
arm group type: Experimental
description: Volunteers will come to the clinical research center. Volunteers will provide a urine sample. The volunteers will be fitted to record an electrocardiogram (ECG) and blood pressure. ECG will be recorded continuously. Blood pressure will be taken at baseline and every 10 minutes thereafter for one hour. The solution with deuterated PGD2 (10 microgram) will be infused over the course of 30 min. Volunteers will be monitored for 1 h after the end of the infusion, and volunteers will start collecting urine in intervals up to 10 h.
Infusion of the deuterated PGD2 solution will be performed in the presence of a physician. The injection solution will be prepared by Vanderbilt University Medical Center (VUMC) Investigational Drug Services. The solution will be sterile and pyrogen free.
intervention type: Dietary Supplement
intervention name: niacin
description: induce biosynthesis of PGD2
arm group label: niacin
arm group label: niacin + low-dose aspirin
arm group label: niacin + regular-strength aspirin
intervention type: Drug
intervention name: aspirin
description: inhibition of cyclooxygenase
arm group label: niacin + low-dose aspirin
arm group label: niacin + regular-strength aspirin
intervention type: Other
intervention name: PGD2
description: labeled precursor
arm group label: deuterated PGD2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Claus M Schneider, PhD
role: Principal Investigator
affiliation: Vanderbilt University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: Claus Schneider
investigator title: Associate Professor of Pharmacology
mesh term: Aspirin
mesh term: Niacin
sharing ipd: Yes
ipd description: IPD (study protocol, informed consent forms) will be shared upon a justified request by an investigator.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: IPD will become available from the beginning of the study until completion.
ipd access criteria: Researchers need to make a justified request.