<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/NCT03295747</url>
  </required_header>
  <id_info>
    <org_study_id>R21AT009101-01</org_study_id>
    <nct_id>NCT03295747</nct_id>
  </id_info>
  <brief_title>Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children With Functional Abdominal Pain</brief_title>
  <acronym>PMO</acronym>
  <official_title>Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children With Functional Abdominal Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Robert Shulman, M.D.</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>
      Aim 1 - Determine the pharmacokinetics of PMO (menthol) of three different doses in children&#xD;
      with functional abdominal pain (FAP) (n=30).&#xD;
&#xD;
      Aim 2 - Determine pharmacodynamic effect of three different doses of PMO on gut microbiome&#xD;
      composition and contractile activity/gut transit rate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Children with functional abdominal pain (FAP) ages 7-12 years (n=30) will be recruited.&#xD;
&#xD;
      The study participants will be admitted to the Children's Nutrition Research Center. A&#xD;
      medical history and a general physical examination performed by the investigator or the&#xD;
      research nurse. The height, weight, and vital signs (pulse rate, respiratory rate, and seated&#xD;
      blood pressure) will be obtained. After application of a topical anesthetic to the site&#xD;
      chosen for study-related blood sampling, a cannula will be inserted e to obtain repeated&#xD;
      blood samples.&#xD;
&#xD;
      At approximately 0900, subjects will receive one of three doses of PMO as a single oral dose.&#xD;
      Immediately prior to administration of the PMO, a blood sample will be obtained to measure&#xD;
      total menthol concentration and leukocytes for isolation of DNA for CYP2A6 and UGT2B7&#xD;
      genotyping.&#xD;
&#xD;
      After PMO administration, repeated blood samples will be obtained over 24 hours.&#xD;
&#xD;
      At 2 hours after PMO administration, participants will be given a standardized meal and will&#xD;
      eat ad libitum thereafter.&#xD;
&#xD;
      After completion of the final (24 hours) blood samples, vital signs will be reassessed and&#xD;
      the venous cannula removed. Parents will receive a follow-up call from the research&#xD;
      coordinator to access/evaluate if any adverse effects from dose or blood sampling received at&#xD;
      the overnight study visit.&#xD;
&#xD;
      Prior to and after administration of peppermint oil (PMO) for 1 week at the dose defined&#xD;
      above, children will undergo measurement of gut microbiome composition and GI motility and&#xD;
      transit time. At the time of the stool collection, the child will also keep a 3 day diet&#xD;
      history.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2017</start_date>
  <completion_date type="Actual">March 28, 2019</completion_date>
  <primary_completion_date type="Actual">March 28, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants randomized to one of three prospective arms as reflected by three treatment doses for the duration of the study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics</measure>
    <time_frame>24 hours</time_frame>
    <description>Area under the curve</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Contractility</measure>
    <time_frame>Prior to and during peppermint oil treatment</time_frame>
    <description>Number and amplitude of gut contractions as measured by SmartPill</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut Microbiome Composition</measure>
    <time_frame>Prior to and during peppermint oil treatment</time_frame>
    <description>Microbiome is defined for this study as a statistically significant change from baseline after treatment with PMO, correcting for multiple testing (q value). Such changes may occur with respect to gut microbiome diversity and/or composition (e.g., phylum, family, genera). We anticipate there will be an increased bacterial diversity, as well as increases in the abundance of organisms associated with a healthy microbiome, in response to PMO administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Motility</measure>
    <time_frame>Prior to and during peppermint oil treatment</time_frame>
    <description>Gut transit time as measured by SmartPill</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Abdominal Pain</condition>
  <arm_group>
    <arm_group_label>180 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>180 mg of peppermint oil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>360 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>360 mg of peppermint oil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>540 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>540 mg of peppermint oil</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Peppermint oil</intervention_name>
    <description>Three doses of peppermint oil will be investigated: 180, 360, 540 mg; i.e. three arms.</description>
    <arm_group_label>180 mg</arm_group_label>
    <arm_group_label>360 mg</arm_group_label>
    <arm_group_label>540 mg</arm_group_label>
    <other_name>Enteric coated peppermint oil capsules</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Children ages 7-12 years old&#xD;
&#xD;
          2. They will be able to complete the protocol&#xD;
&#xD;
          3. A child will be recruited if the medical evaluation reveals no organic reason for the&#xD;
             abdominal pain&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Children who have had past bowel surgery;&#xD;
&#xD;
          2. A child with documented GI disorders (e.g., Crohn's disease);&#xD;
&#xD;
          3. A child with a serious chronic medical condition (e.g., diabetes);&#xD;
&#xD;
          4. A child with a weight and/or height &lt; 2 SD for age;&#xD;
&#xD;
          5. Children with chronic conditions with GI symptoms (e.g., cystic fibrosis);&#xD;
&#xD;
          6. Children with autism spectrum disorder, significant developmental delay, psychosis,&#xD;
             depression, or a history of bipolar disorder;&#xD;
&#xD;
          7. Children who have been treated with antibiotics/probiotics within 2 mo. (because of&#xD;
             effects on microbiome analysis).&#xD;
&#xD;
          8. Children who speak only Spanish&#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>Shulman J. Shulman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Texas Children's Hospital</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>
  <results_reference>
    <citation>Shulman RJ, Chumpitazi BP, Abdel-Rahman SM, Garg U, Musaad S, Kearns GL. Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain. Br J Clin Pharmacol. 2022 Mar;88(3):1321-1333. doi: 10.1111/bcp.15076. Epub 2021 Oct 19. Erratum In: Br J Clin Pharmacol. 2022 Dec;88(12):5436.</citation>
    <PMID>34528282</PMID>
  </results_reference>
  <results_reference>
    <citation>Thapa S, Luna RA, Chumpitazi BP, Oezguen N, Abdel-Rahman SM, Garg U, Musaad S, Versalovic J, Kearns GL, Shulman RJ. Peppermint oil effects on the gut microbiome in children with functional abdominal pain. Clin Transl Sci. 2022 Apr;15(4):1036-1049. doi: 10.1111/cts.13224. Epub 2022 Jan 20.</citation>
    <PMID>35048535</PMID>
  </results_reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>April 1, 2022</last_update_submitted>
  <last_update_submitted_qc>April 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-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>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03295747/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03295747
org study id: R21AT009101-01
nct id: NCT03295747
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Aim 1 - Determine the pharmacokinetics of PMO (menthol) of three different doses in children
      with functional abdominal pain (FAP) (n=30).

      Aim 2 - Determine pharmacodynamic effect of three different doses of PMO on gut microbiome
      composition and contractile activity/gut transit rate.
Children with functional abdominal pain (FAP) ages 7-12 years (n=30) will be recruited.

      The study participants will be admitted to the Children's Nutrition Research Center. A
      medical history and a general physical examination performed by the investigator or the
      research nurse. The height, weight, and vital signs (pulse rate, respiratory rate, and seated
      blood pressure) will be obtained. After application of a topical anesthetic to the site
      chosen for study-related blood sampling, a cannula will be inserted e to obtain repeated
      blood samples.

      At approximately 0900, subjects will receive one of three doses of PMO as a single oral dose.
      Immediately prior to administration of the PMO, a blood sample will be obtained to measure
      total menthol concentration and leukocytes for isolation of DNA for CYP2A6 and UGT2B7
      genotyping.

      After PMO administration, repeated blood samples will be obtained over 24 hours.

      At 2 hours after PMO administration, participants will be given a standardized meal and will
      eat ad libitum thereafter.

      After completion of the final (24 hours) blood samples, vital signs will be reassessed and
      the venous cannula removed. Parents will receive a follow-up call from the research
      coordinator to access/evaluate if any adverse effects from dose or blood sampling received at
      the overnight study visit.

      Prior to and after administration of peppermint oil (PMO) for 1 week at the dose defined
      above, children will undergo measurement of gut microbiome composition and GI motility and
      transit time. At the time of the stool collection, the child will also keep a 3 day diet
      history.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants randomized to one of three prospective arms as reflected by three treatment doses for the duration of the study.
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetics
time frame: 24 hours
description: Area under the curve
measure: Contractility
time frame: Prior to and during peppermint oil treatment
description: Number and amplitude of gut contractions as measured by SmartPill
measure: Gut Microbiome Composition
time frame: Prior to and during peppermint oil treatment
description: Microbiome is defined for this study as a statistically significant change from baseline after treatment with PMO, correcting for multiple testing (q value). Such changes may occur with respect to gut microbiome diversity and/or composition (e.g., phylum, family, genera). We anticipate there will be an increased bacterial diversity, as well as increases in the abundance of organisms associated with a healthy microbiome, in response to PMO administration.
measure: Motility
time frame: Prior to and during peppermint oil treatment
description: Gut transit time as measured by SmartPill
arm group label: 180 mg
arm group type: Experimental
description: 180 mg of peppermint oil
arm group label: 360 mg
arm group type: Experimental
description: 360 mg of peppermint oil
arm group label: 540 mg
arm group type: Experimental
description: 540 mg of peppermint oil
intervention type: Drug
intervention name: Peppermint oil
description: Three doses of peppermint oil will be investigated: 180, 360, 540 mg; i.e. three arms.
arm group label: 180 mg
arm group label: 360 mg
arm group label: 540 mg
other name: Enteric coated peppermint oil capsules
criteria: 
gender: All
minimum age: 7 Years
maximum age: 12 Years
healthy volunteers: No
last name: Shulman J. Shulman, MD
role: Principal Investigator
affiliation: Baylor College of Medicine
facility: 
country: United States
citation: Shulman RJ, Chumpitazi BP, Abdel-Rahman SM, Garg U, Musaad S, Kearns GL. Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain. Br J Clin Pharmacol. 2022 Mar;88(3):1321-1333. doi: 10.1111/bcp.15076. Epub 2021 Oct 19. Erratum In: Br J Clin Pharmacol. 2022 Dec;88(12):5436.
PMID: 34528282
citation: Thapa S, Luna RA, Chumpitazi BP, Oezguen N, Abdel-Rahman SM, Garg U, Musaad S, Versalovic J, Kearns GL, Shulman RJ. Peppermint oil effects on the gut microbiome in children with functional abdominal pain. Clin Transl Sci. 2022 Apr;15(4):1036-1049. doi: 10.1111/cts.13224. Epub 2022 Jan 20.
PMID: 35048535
responsible party type: Sponsor-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
sharing ipd: No
provided document: 