Peppermint Oil Pharmacokinetics/Dynamics

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

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)

Study Overview

• Status: Withdrawn
• Conditions: Abdominal Pain
• Intervention / Treatment: Drug: Peppermint oil

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Children's Nutrition Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Robert J Shulman, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2020
• Primary Completion (Actual): September 14, 2023
• Study Completion (Actual): September 14, 2023

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Abdominal Pain; Physiological Effects of Drugs; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipruritics; Peppermint oil; Menthol
• Other Study ID Numbers: H-40351

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No