Peppermint Oil Pharmacokinetics/Dynamics

Study Overview
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Brief Summary
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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: Microbiome composition (16S RNA sequencing) 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)

Detailed Description
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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.

Official Title
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Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children With Functional Abdominal Pain

Conditions
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Abdominal Pain

Intervention / Treatment
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* Drug: Peppermint oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children ages 7-12 years who are able to assent to the procedures Able to complete the diaries which have been validated for use in this age range The history and medical evaluation reveal no organic reason for the abdominal pain The child has abdominal pain that meets the definition of FAP according to pediatric Rome IV Ability to understand study procedures and to comply with them for the entire length of the study Childrens' body weights will not vary by more than 10-15 kg (so that dose per kg is comparable within the two dosing groups) Exclusion Criteria: Past bowel surgery Documented GI disorders (e.g., Crohn's disease) A serious chronic medical condition (e.g., diabetes) A weight and/or height < 2 SD for age Chronic conditions with GI symptoms (e.g., cystic fibrosis) Autism spectrum disorder, significant developmental delay, psychosis, depression, or a history of bipolar disorder Antibiotic/probiotic treatment within 2 mo. Allergy/sensitivity to PMO or its ingredients Inability to swallow the PMO capsule or the SmartPill® Inability to speak English - testing materials are available only in this language Unable to discontinue laxative, prokinetic, or neuromodulator from 3 wk prior to Visit 1 through the end of the study

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 540 mg<br>Peppermint oil at a dose of 180 mg thrice daily orally | Drug: Peppermint oil<br>* Administration of peppermint oil at one of two daily doses.<br>* Other names: menthol;|
| Experimental: 900 mg<br>Peppermint oil at a dose of 180 mg five times daily orally | Drug: Peppermint oil<br>* Administration of peppermint oil at one of two daily doses.<br>* Other names: menthol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of peppermint oil | Area under the curve | 2 weeks | 
| Gut Microbiome composition | Gut microbiome composition as determined by 16S sequencing as a consequence of the administration of peppermint oil at the two doses given. | 2 weeks | 
| Gut transit time | Gut transit time as a consequence of the administration of peppermint oil at the two doses given. | 2 weeks | 
| Gut contractility | Gut contractility as a consequence of the administration of peppermint oil at the two doses given. | 2 weeks |