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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-004195-32 | EudraCT Number |
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| Name | Class |
|---|---|
| ZonMw: The Netherlands Organisation for Health Research and Development | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tempocol-ColoPulse® | Experimental | Tempocol-ColoPulse® is a colon-targeted-delivery peppermint oil capsule that will deliver peppermint oil in the (ileo-) colonic region specifically. |
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| Tempocol® | Active Comparator | Tempocol® is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule) | Drug | Peppermint oil capsule available as an over the counter prescription drug on the Dutch market. |
|
| Measure | Description | Time Frame |
|---|---|---|
| T-max | Time to reach maximum menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) concentration in plasma | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| C-max | Menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) peak plasma concentrations | 24 hours |
| T-lag | Time until a measurable plasma concentration of menthol-glucuronide occurs after oral administration of peppermint oil (45ug/L) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| A Masclee, Prof, PhD, MD | Maastricht University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University Medical Center | Maastricht | Limburg | 5800 | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24096020 | Background | 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. | |
| 20621586 |
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This was a crossover design.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ileocolonic Release PO First, Then Small-intestinal Release Peppermint Oil | Ileocolonic release PO is a targeted ileocolonic release peppermint oil capsule that releases peppermint oil in the (ileo-) colonic region specifically. Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule): Peppermint oil capsule with a coating developed according to the ColoPulse® technology, ensuring a pulsatile and therefore slower release in a lower part of the intestinal tract compared to Tempocol, namely in the (ileo-)colonic region. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule) | Drug | Peppermint oil capsule with a coating developed according to the ColoPulse® technology, ensuring a pulsatile and therefore slower release in a lower part of the intestinal tract compared to Tempocol, namely in the (ileo-)colonic region. |
|
|
| 24 hours |
| AUC | Area under the plasma concentration-time curve from t=0 hrs until t=24 hrs. | 24 hours |
| T1/2 | elimination half-life; time required for the plasma concentration of menthol-glucuronide to reach half of its original value. | 24 hours |
| Menthol-glucuronide Urine Exretion Time Curve | 24 hours |
| L-Menthol Concentration in Feces | +/- 24 hours |
| Difference in Total Number of Side Effects Per Time Point. | 24 hours |
| Tolerability Assessed by Heart Rate, Blood Pressure and Reported Side Effects | Assessed by heart rate, blood pressure and reported side effects. | 24 hours |
| Background |
| 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. |
| 24100754 | Background | 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. |
| 21833945 | Background | 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. |
| 30284674 | Result | 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. |
| FG001 | Small Intestinal Release PO First, Then Ileocolonic Release Peppermint Oil | Small Intestinal Release PO (Tempocol®) is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine. Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule): Peppermint oil capsule available as an over the counter prescription drug on the Dutch market. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Ileocolonic Release PO on First Test Day | Ileocolonic release PO is a targeted ileocolonic release peppermint oil capsule that releases peppermint oil in the (ileo-) colonic region specifically. Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule): Peppermint oil capsule with a coating developed according to the ColoPulse® technology, ensuring a pulsatile and therefore slower release in a lower part of the intestinal tract compared to Tempocol, namely in the (ileo-)colonic region. |
| BG001 | Small Intestinal Release PO on First Test Day | Small Intestinal Release PO (Tempocol®) is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine. Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule): Peppermint oil capsule available as an over the counter prescription drug on the Dutch market. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| BMI | Median | Inter-Quartile Range | kg/m^2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | T-max | Time to reach maximum menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) concentration in plasma | Posted | Median | Inter-Quartile Range | minutes | 24 hours |
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| Secondary | C-max | Menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) peak plasma concentrations | Posted | Median | Inter-Quartile Range | ug/L | 24 hours |
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| Secondary | T-lag | Time until a measurable plasma concentration of menthol-glucuronide occurs after oral administration of peppermint oil (45ug/L) | Posted | Median | Inter-Quartile Range | minutes | 24 hours |
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| Secondary | AUC | Area under the plasma concentration-time curve from t=0 hrs until t=24 hrs. | Posted | Median | Inter-Quartile Range | ug*h/L | 24 hours |
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| Secondary | T1/2 | elimination half-life; time required for the plasma concentration of menthol-glucuronide to reach half of its original value. | Posted | Median | Inter-Quartile Range | hours | 24 hours |
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| Secondary | Menthol-glucuronide Urine Exretion Time Curve | No urine analysis was performed due to lack in funding. In addition, it was felt that the systemic concentration of menthol glucuronide concentration provided enough information to answer the research question. | Posted | 24 hours |
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| Secondary | L-Menthol Concentration in Feces | Not Posted | +/- 24 hours | Participants | |||||||||||||||||||||||||||||||||||
| Secondary | Difference in Total Number of Side Effects Per Time Point. | Not Posted | 24 hours | Participants | |||||||||||||||||||||||||||||||||||
| Secondary | Tolerability Assessed by Heart Rate, Blood Pressure and Reported Side Effects | Assessed by heart rate, blood pressure and reported side effects. | Not Posted | 24 hours | Participants |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ileocolonic Release PO | Ileocolonic release PO is a targeted ileocolonic release peppermint oil capsule that releases peppermint oil in the (ileo-) colonic region specifically. Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule): Peppermint oil capsule with a coating developed according to the ColoPulse® technology, ensuring a pulsatile and therefore slower release in a lower part of the intestinal tract compared to Tempocol, namely in the (ileo-)colonic region. | 0 | 8 | 4 | 8 | ||
| EG001 | Small Intestinal Release PO | Small Intestinal Release PO (Tempocol®) is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine. Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule): Peppermint oil capsule available as an over the counter prescription drug on the Dutch market. | 0 | 8 | 2 | 8 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acid regurgitation | Gastrointestinal disorders | Systematic Assessment |
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| Fecal urgency | Gastrointestinal disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Altered Fecal Odor | Gastrointestinal disorders | Systematic Assessment | Peppermint odor |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Z. Weerts | Maastricht University (Medical Center) | z.weerts@maastrichtuniversity.nl |
| ID | Term |
|---|---|
| D043183 | Irritable Bowel Syndrome |
| D015746 | Abdominal Pain |
| D003108 | Colonic Diseases |
| D059265 | Visceral Pain |
| ID | Term |
|---|---|
| D003109 | Colonic Diseases, Functional |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012817 | Signs and Symptoms, Digestive |
| D059226 | Nociceptive Pain |
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| ID | Term |
|---|---|
| C015424 | peppermint oil |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Participants |
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