Clinical trial NCT02291445: Comparing a 182mg Colon-targeted-delivery Peppermint Oil Capsule (Tempocol-ColoPulse®) and a 182mg Enteric-coated Peppermint Oil Capsule (Tempocol®), a Pharmacokinetic Study
Official title: A Randomized, Double Blind, Single Dose, Two Treatment, Two Period Crossover Pharmacokinetic Study Comparing a 182mg Colon-targeted-delivery Peppermint Oil Capsule (Tempocol-ColoPulse®) and a 182mg Enteric-coated Peppermint Oil Capsule (Tempocol®) in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome
Abdominal Pain
Colonic Diseases
Visceral Pain
Keywords: Peppermint oil
Menthol
Volatile oil
Plant oil
Visceral pain
Abdominal pain
Irritable bowel syndrome (IBS)
Colonic disease
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2014-11-14
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is a pilot study to compare the relative bioavailability between two peppermint oil formulations, namely a ileocolonic release peppermint oil and an small intestinal release peppermint oil (Tempocol®). This study is conducted as part of a future multicenter randomized controlled trial that will assess the therapeutic effect of the new peppermint oil formulation in IBS patients.

Detailed description: Rationale: Peppermint oil has shown to be effective in the treatment of IBS symptoms in several meta-analyses. However, the level of evidence is moderate and peppermint oil remains relatively under-used in IBS. Therefore the investigators plan to conduct a multicenter randomized controlled trial to investigate the possible beneficial effects of peppermint oil in IBS. To improve efficacy and to reduce side effects, the investigators aim to study the use of a new peppermint oil formulation that will slowly release the oil in the (ileo-) colonic region specifically. In order to demonstrate differences in pharmacokinetics, the subsidizing party, ZonMW, requested an additional pilot study (described in the present protocol) in which the investigators will investigate surrogate markers for local colon bioavailability, tolerability and side effects of the new ileocolonic release PO.

Study design: a randomized, double blind, two-period, two-treatment crossover study with a wash out period of at least 14 days.

Intervention: All study volunteers will receive a single dose of 182mg of both ileocolonic release peppermint oil and small intestinal release peppermint oil, each on a different test day.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Subjects may be confronted with certain inconveniences and minor risks. They are required to visit the MUMC+ 5 times, once for the screening and two times per test day for various non-invasive measurements (questionnaires, blood pressure and heart-rate measurement, urine and fecal sampling, pregnancy test in women in fertile ages, general physical exam) as well as for minor invasive venous blood sampling, after which a small haematoma can occur. Total time investment is +/- 30 hours, subjects will not benefit from participation.

Eligibility criteria: Inclusion Criteria:

* Based on medical history and previous examination, no gastrointestinal complaints can be defined
* Age between 18 and 65 years
* BMI between 18 and 25 kg/m2 and a weight of at least 50 kilograms
* Women in fertile age (\<55 years old) must use contraception or be postmenopausal for at least two years

Exclusion Criteria:

* History of severe or chronic cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol
* Use of medication, including vitamin and iron supplementation, except oral contraceptives, within 14 days prior to start of the study
* Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study
* Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgment of the principle investigator)
* Dieting (for example lactose-free, gluten-free, caloric-restrictive, vegetarian or vegan, macrobiotic diet)
* Pregnancy, lactation
* High alcohol consumption (\>15 alcoholic consumptions per week)
* Smoking/ Using drugs of abuse
* Self-admitted HIV-positive state
* Known allergic reaction to peppermint
* High intake of caffeine (\>8 cups coffee a day)

Primary outcomes:
measure: T-max
timeFrame: 24 hours
Secondary outcomes:
measure: C-max
timeFrame: 24 hours
measure: T-lag
timeFrame: 24 hours
measure: AUC
timeFrame: 24 hours
measure: T1/2
timeFrame: 24 hours
measure: Menthol-glucuronide Urine Exretion Time Curve
timeFrame: 24 hours
measure: L-Menthol Concentration in Feces
timeFrame: +/- 24 hours
measure: Difference in Total Number of Side Effects Per Time Point.
timeFrame: 24 hours
measure: Tolerability Assessed by Heart Rate, Blood Pressure and Reported Side Effects
timeFrame: 24 hours
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: A Masclee, Prof, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maurer JM, Schellekens RC, van Rieke HM, Stellaard F, Wutzke KD, Buurman DJ, Dijkstra G, Woerdenbag HJ, Frijlink HW, Kosterink JG. ColoPulse tablets perform comparably in healthy volunteers and Crohn's patients and show no influence of food and time of food intake on bioavailability. J Control Release. 2013 Dec 28;172(3):618-24. doi: 10.1016/j.jconrel.2013.09.021. Epub 2013 Oct 2.
citation: Schellekens RC, Stellaard F, Olsder GG, Woerdenbag HJ, Frijlink HW, Kosterink JG. Oral ileocolonic drug delivery by the colopulse-system: a bioavailability study in healthy volunteers. J Control Release. 2010 Sep 15;146(3):334-40. doi: 10.1016/j.jconrel.2010.05.028. Epub 2010 May 31.
citation: Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014 Jul;48(6):505-12. doi: 10.1097/MCG.0b013e3182a88357.
citation: Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011 Aug 10;2011(8):CD003460. doi: 10.1002/14651858.CD003460.pub3.
citation: Weerts ZZRM, Keszthelyi D, Vork L, Aendekerk NCP, Frijlink HW, Brouwers JRBJ, Neef C, Jonkers DMAE, Masclee AAM. A Novel Ileocolonic Release Peppermint Oil Capsule for Treatment of Irritable Bowel Syndrome: A Phase I Study in Healthy Volunteers. Adv Ther. 2018 Nov;35(11):1965-1978. doi: 10.1007/s12325-018-0802-1. Epub 2018 Oct 4.