Irritable Bowel SyndromePhase 2NCT02291445

Comparing a 182mg Colon-targeted-delivery Peppermint Oil Capsule (Tempocol-ColoPulse®) and a 182mg Enteric-coated Peppermint Oil Capsule (Tempocol®), a Pharmacokinetic Study

A Phase 2 study testing Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule) and Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule) in people with Irritable Bowel Syndrome and Abdominal Pain, run by Maastricht University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Irritable Bowel Syndrome, Abdominal Pain, Colonic Diseases
What is being tested?: Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule) and Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteNetherlands
Study dates: Mar 2015to Sep 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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)

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

Maastricht University Medical Center
Maastricht, Limburg, 5800

Other trials in Netherlands

About this 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

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.

Read the 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.

Conditions: Irritable Bowel Syndrome, Abdominal Pain, Colonic Diseases, Visceral Pain
Being tested: Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule), Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)
Keywords: Peppermint oil, Menthol, Volatile oil, Plant oil, Visceral pain, Abdominal pain, Irritable bowel syndrome (IBS), Colonic disease
Medical subject headings: Irritable Bowel Syndrome, Abdominal Pain, Colonic Diseases, Visceral Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)Drug
Also called Tempocol® (CBG-rvg number 109856)
Peppermint oil capsule available as an over the counter prescription drug on the Dutch market.
Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)Drug
Also called Tempocol-ColoPulse®
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.

Study groups in NCT02291445
Study group	Role	What they receive
Tempocol-ColoPulse®	Experimental	Tempocol-ColoPulse® is a colon-targeted-delivery peppermint oil capsule that will deliver peppermint oil in the (ileo-) colonic region specifically. Receives: Drug: Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)
Tempocol®	Active comparator	Tempocol® is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine. Receives: Drug: Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)

What is being measured

The primary outcome is the main question the study is designed to answer.

T-max
Time to reach maximum menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) concentration in plasma
Measured: 24 hours

Secondary outcomes (8)

C-max
Menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) peak plasma concentrations
Measured: 24 hours
T-lag
Time until a measurable plasma concentration of menthol-glucuronide occurs after oral administration of peppermint oil (45ug/L)
Measured: 24 hours
AUC
Area under the plasma concentration-time curve from t=0 hrs until t=24 hrs.
Measured: 24 hours
T1/2
elimination half-life; time required for the plasma concentration of menthol-glucuronide to reach half of its original value.
Measured: 24 hours
Menthol-glucuronide Urine Exretion Time Curve
Measured: 24 hours
L-Menthol Concentration in Feces
Measured: +/- 24 hours
Difference in Total Number of Side Effects Per Time Point.
Measured: 24 hours
Tolerability Assessed by Heart Rate, Blood Pressure and Reported Side Effects
Assessed by heart rate, blood pressure and reported side effects.
Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2015Sep 2015

First posted14 Nov 2014 (estimated)
Study startMar 2015
Primary completionJul 2015
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02291445
Sponsor's protocol ID: 50941
Other IDs: 2014-004195-32, 2014
Status last verified: Jul 2015
First submitted: 11 Nov 2014
Last updated: 24 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 24096020
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.
PubMed 20621586
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.
PubMed 24100754
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.
PubMed 21833945
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.
PubMed 30284674

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 24 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02291445
Acronym / sponsor ID: 50941
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
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: Maastricht University Medical CenterUniversity, hospital or other
Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
Study start: Mar 2015
Primary completion: Jul 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 14 Nov 2014 (estimated)
Results: Posted 24 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Tempocol-ColoPulse®	Experimental	Drug: Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)Tempocol-ColoPulse® is a colon-targeted-delivery peppermint oil capsule that will deliver peppermint oil in the (ileo-) colonic region specifically.
Tempocol®	Active comparator	Drug: Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)Tempocol® is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (11 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)Also: Tempocol® (CBG-rvg number 109856)Peppermint oil capsule available as an over the counter prescription drug on the Dutch market.	Drug	Tempocol®
Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)Also: Tempocol-ColoPulse®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.	Drug	Tempocol-ColoPulse®

Primary outcome

T-max
Time frame: 24 hours
Time to reach maximum menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) concentration in plasma

8 secondary outcomes

C-max
Time frame: 24 hours
T-lag
Time frame: 24 hours
AUC
Time frame: 24 hours
T1/2
Time frame: 24 hours
Menthol-glucuronide Urine Exretion Time Curve
Time frame: 24 hours
L-Menthol Concentration in Feces
Time frame: +/- 24 hours
Difference in Total Number of Side Effects Per Time Point.
Time frame: 24 hours
Tolerability Assessed by Heart Rate, Blood Pressure and Reported Side Effects
Time frame: 24 hours

Results and safety

Results posted to the registry on 24 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ileocolonic Release PO First, Then Small-intestinal Release Peppermint Oil	4	4
Small Intestinal Release PO First, Then Ileocolonic Release Peppermint Oil	4	4

Primary outcome: T-max

Time frame: 24 hours. Median (Inter-Quartile Range). Unit: minutes

Measure	Ileocolonic Release PO n = 8	Small Intestinal Release PO n = 8
Value	360 (360 to 405)	180 (120 to 180)

8 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ileocolonic Release PO	0 of 8 (0%)	4 of 8 (50%)	Not reported
Small Intestinal Release PO	0 of 8 (0%)	2 of 8 (25%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24096020Maurer 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.
Background: PubMed 20621586Schellekens 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.
Background: PubMed 24100754Khanna 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.
Background: PubMed 21833945Ruepert 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.
Results publication: PubMed 30284674Weerts 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

A Masclee, Prof, PhD, MD principal investigator

Maastricht University Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

T-max (time frame: 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02291445, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2022; AzTrials last refreshed its copy on 1 Nov 2026.