Clinical trial NCT04497870: Peppermint Oil Pharmacokinetics/Dynamics
Official title: Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children With Functional Abdominal Pain
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Abdominal Pain
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2020-08-04
Enrollment: 0
Sex: ALL
Minimum age (years): 7
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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)

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics of peppermint oil
timeFrame: 2 weeks
measure: Gut Microbiome composition
timeFrame: 2 weeks
measure: Gut transit time
timeFrame: 2 weeks
measure: Gut contractility
timeFrame: 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: Children's Nutrition Research Center
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Robert J Shulman, MD
role: PRINCIPAL_INVESTIGATOR
References: