Clinical trial NCT03295747: Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children With Functional Abdominal Pain
Official title: Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children With Functional Abdominal Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Abdominal Pain
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2017-09-28
Enrollment: 30
Sex: ALL
Minimum age (years): 7
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Children ages 7-12 years old
2. They will be able to complete the protocol
3. A child will be recruited if the medical evaluation reveals no organic reason for the abdominal pain

Exclusion Criteria:

1. Children who have had past bowel surgery;
2. A child with documented GI disorders (e.g., Crohn's disease);
3. A child with a serious chronic medical condition (e.g., diabetes);
4. A child with a weight and/or height \< 2 SD for age;
5. Children with chronic conditions with GI symptoms (e.g., cystic fibrosis);
6. Children with autism spectrum disorder, significant developmental delay, psychosis, depression, or a history of bipolar disorder;
7. Children who have been treated with antibiotics/probiotics within 2 mo. (because of effects on microbiome analysis).
8. Children who speak only Spanish

Primary outcomes:
measure: Pharmacokinetics
timeFrame: 24 hours
Secondary outcomes:
measure: Contractility
timeFrame: Prior to and during peppermint oil treatment
measure: Gut Microbiome Composition
timeFrame: Prior to and during peppermint oil treatment
measure: Motility
timeFrame: Prior to and during peppermint oil treatment
Other outcomes:
Locations:
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Shulman J. Shulman, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.