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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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 old They will be able to complete the protocol A child will be recruited if the medical evaluation reveals no organic reason for the abdominal pain Exclusion Criteria: Children who have had past bowel surgery; A child with documented GI disorders (e.g., Crohn's disease); A child with a serious chronic medical condition (e.g., diabetes); A child with a weight and/or height < 2 SD for age; Children with chronic conditions with GI symptoms (e.g., cystic fibrosis); Children with autism spectrum disorder, significant developmental delay, psychosis, depression, or a history of bipolar disorder; Children who have been treated with antibiotics/probiotics within 2 mo. (because of effects on microbiome analysis). Children who speak only Spanish

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants randomized to one of three prospective arms as reflected by three treatment doses for the duration of the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 180 mg<br>180 mg of peppermint oil | Drug: Peppermint oil<br>* Three doses of peppermint oil will be investigated: 180, 360, 540 mg; i.e. three arms.<br>* Other names: Enteric coated peppermint oil capsules;|
| Experimental: 360 mg<br>360 mg of peppermint oil | Drug: Peppermint oil<br>* Three doses of peppermint oil will be investigated: 180, 360, 540 mg; i.e. three arms.<br>* Other names: Enteric coated peppermint oil capsules;|
| Experimental: 540 mg<br>540 mg of peppermint oil | Drug: Peppermint oil<br>* Three doses of peppermint oil will be investigated: 180, 360, 540 mg; i.e. three arms.<br>* Other names: Enteric coated peppermint oil capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | Area under the curve | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Contractility | Number and amplitude of gut contractions as measured by SmartPill | Prior to and during peppermint oil treatment | 
| Gut Microbiome Composition | 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. | Prior to and during peppermint oil treatment | 
| Motility | Gut transit time as measured by SmartPill | Prior to and during peppermint oil treatment |