<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/NCT04497870</url>
  </required_header>
  <id_info>
    <org_study_id>H-40351</org_study_id>
    <nct_id>NCT04497870</nct_id>
  </id_info>
  <brief_title>Peppermint Oil Pharmacokinetics/Dynamics</brief_title>
  <official_title>Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children With Functional Abdominal Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Baylor College of Medicine</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>
      In children 7-12 years of age with functional abdominal pain (n=42) determine:&#xD;
&#xD;
      Aim 1 - To examine and characterize the threshold of the exposure (PK) vs. response (PD)&#xD;
      relationship of PMO (menthol)&#xD;
&#xD;
      Aim 2 - PD of PMO as assessed by:&#xD;
&#xD;
        1. Microbiome composition (16S RNA sequencing)&#xD;
&#xD;
        2. Transit rate/contractile activity (using the SmartPill®) Aim 3 - Evaluate the potential&#xD;
           association between PD response and clinical symptoms (abdominal pain and stooling&#xD;
           pattern via validated diary), psychosocial distress (anxiety, depression, somatization),&#xD;
           and characterize potential side effects (questionnaire)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An initial single-dose PK study will be carried out. Forty-two children (n=21 per dose) will&#xD;
      be randomized to receive approximately 10.9 mg·kg-1·d-1 of PMO or to receive approximately&#xD;
      18.2 mg·kg-1·d-1 (1.67-fold the median dose).&#xD;
&#xD;
      Following the single-dose PK study, a PD study will be carried out wherein the subjects will&#xD;
      receive their assigned dose of PMO for 7 days.&#xD;
&#xD;
      At baseline (before the PK study) and after the PK study (i.e., during the PD study),&#xD;
      subjects will keep a pain and stooling diary, collect stool for microbiome analysis, and&#xD;
      swallow a SmartPill to measure gut motility and transit time. At baseline only, anxiety,&#xD;
      depression, somatization will be measured. During the PD study, any side effects will be&#xD;
      recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    This study was superseded by NCT03295747&#xD;
  </why_stopped>
  <start_date type="Actual">July 9, 2020</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of peppermint oil</measure>
    <time_frame>2 weeks</time_frame>
    <description>Area under the curve</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gut Microbiome composition</measure>
    <time_frame>2 weeks</time_frame>
    <description>Gut microbiome composition as determined by 16S sequencing as a consequence of the administration of peppermint oil at the two doses given.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gut transit time</measure>
    <time_frame>2 weeks</time_frame>
    <description>Gut transit time as a consequence of the administration of peppermint oil at the two doses given.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gut contractility</measure>
    <time_frame>2 weeks</time_frame>
    <description>Gut contractility as a consequence of the administration of peppermint oil at the two doses given.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Abdominal Pain</condition>
  <arm_group>
    <arm_group_label>540 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Peppermint oil at a dose of 180 mg thrice daily orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>900 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Peppermint oil at a dose of 180 mg five times daily orally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Peppermint oil</intervention_name>
    <description>Administration of peppermint oil at one of two daily doses.</description>
    <arm_group_label>540 mg</arm_group_label>
    <arm_group_label>900 mg</arm_group_label>
    <other_name>menthol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children ages 7-12 years who are able to assent to the procedures&#xD;
&#xD;
          -  Able to complete the diaries which have been validated for use in this age range&#xD;
&#xD;
          -  The history and medical evaluation reveal no organic reason for the abdominal pain&#xD;
&#xD;
          -  The child has abdominal pain that meets the definition of FAP according to pediatric&#xD;
             Rome IV&#xD;
&#xD;
          -  Ability to understand study procedures and to comply with them for the entire length&#xD;
             of the study&#xD;
&#xD;
          -  Childrens' body weights will not vary by more than 10-15 kg (so that dose per kg is&#xD;
             comparable within the two dosing groups)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Past bowel surgery&#xD;
&#xD;
          -  Documented GI disorders (e.g., Crohn's disease)&#xD;
&#xD;
          -  A serious chronic medical condition (e.g., diabetes)&#xD;
&#xD;
          -  A weight and/or height &lt; 2 SD for age&#xD;
&#xD;
          -  Chronic conditions with GI symptoms (e.g., cystic fibrosis)&#xD;
&#xD;
          -  Autism spectrum disorder, significant developmental delay, psychosis, depression, or a&#xD;
             history of bipolar disorder&#xD;
&#xD;
          -  Antibiotic/probiotic treatment within 2 mo.&#xD;
&#xD;
          -  Allergy/sensitivity to PMO or its ingredients&#xD;
&#xD;
          -  Inability to swallow the PMO capsule or the SmartPill®&#xD;
&#xD;
          -  Inability to speak English - testing materials are available only in this language&#xD;
&#xD;
          -  Unable to discontinue laxative, prokinetic, or neuromodulator from 3 wk prior to Visit&#xD;
             1 through the end of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert J Shulman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Nutrition Research Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>February 13, 2023</last_update_submitted>
  <last_update_submitted_qc>February 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Baylor College of Medicine</investigator_affiliation>
    <investigator_full_name>Robert Shulman, M.D.</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abdominal Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peppermint oil</mesh_term>
    <mesh_term>Menthol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04497870
org study id: H-40351
nct id: NCT04497870
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In children 7-12 years of age with functional abdominal pain (n=42) determine:

      Aim 1 - To examine and characterize the threshold of the exposure (PK) vs. response (PD)
      relationship of PMO (menthol)

      Aim 2 - PD of PMO as assessed by:

        1. Microbiome composition (16S RNA sequencing)

        2. Transit rate/contractile activity (using the SmartPill®) Aim 3 - Evaluate the potential
           association between PD response and clinical symptoms (abdominal pain and stooling
           pattern via validated diary), psychosocial distress (anxiety, depression, somatization),
           and characterize potential side effects (questionnaire)
An initial single-dose PK study will be carried out. Forty-two children (n=21 per dose) will
      be randomized to receive approximately 10.9 mg·kg-1·d-1 of PMO or to receive approximately
      18.2 mg·kg-1·d-1 (1.67-fold the median dose).

      Following the single-dose PK study, a PD study will be carried out wherein the subjects will
      receive their assigned dose of PMO for 7 days.

      At baseline (before the PK study) and after the PK study (i.e., during the PD study),
      subjects will keep a pain and stooling diary, collect stool for microbiome analysis, and
      swallow a SmartPill to measure gut motility and transit time. At baseline only, anxiety,
      depression, somatization will be measured. During the PD study, any side effects will be
      recorded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacokinetics of peppermint oil
time frame: 2 weeks
description: Area under the curve
measure: Gut Microbiome composition
time frame: 2 weeks
description: Gut microbiome composition as determined by 16S sequencing as a consequence of the administration of peppermint oil at the two doses given.
measure: Gut transit time
time frame: 2 weeks
description: Gut transit time as a consequence of the administration of peppermint oil at the two doses given.
measure: Gut contractility
time frame: 2 weeks
description: Gut contractility as a consequence of the administration of peppermint oil at the two doses given.
arm group label: 540 mg
arm group type: Active Comparator
description: Peppermint oil at a dose of 180 mg thrice daily orally
arm group label: 900 mg
arm group type: Experimental
description: Peppermint oil at a dose of 180 mg five times daily orally
intervention type: Drug
intervention name: Peppermint oil
description: Administration of peppermint oil at one of two daily doses.
arm group label: 540 mg
arm group label: 900 mg
other name: menthol
criteria: 
gender: All
minimum age: 7 Years
maximum age: 12 Years
healthy volunteers: No
last name: Robert J Shulman, MD
role: Principal Investigator
affiliation: Baylor College of Medicine
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Baylor College of Medicine
investigator full name: Robert Shulman, M.D.
investigator title: Professor
mesh term: Abdominal Pain
mesh term: Peppermint oil
mesh term: Menthol
sharing ipd: No