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

Primary Purpose

Irritable Bowel Syndrome, Abdominal Pain, Colonic Diseases

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)
Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)
Sponsored by
Maastricht University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Irritable Bowel Syndrome focused on measuring Peppermint oil, Menthol, Volatile oil, Plant oil, Visceral pain, Abdominal pain, Irritable bowel syndrome (IBS), Colonic disease

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Maastricht University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tempocol-ColoPulse®

Tempocol®

Arm Description

Tempocol-ColoPulse® is a colon-targeted-delivery peppermint oil capsule that will deliver peppermint oil in the (ileo-) colonic region specifically.

Tempocol® is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
November 11, 2014
Last Updated
November 15, 2021
Sponsor
Maastricht University Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT02291445
Brief Title
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

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tempocol-ColoPulse®
Arm Type
Experimental
Arm Description
Tempocol-ColoPulse® is a colon-targeted-delivery peppermint oil capsule that will deliver peppermint oil in the (ileo-) colonic region specifically.
Arm Title
Tempocol®
Arm Type
Active Comparator
Arm Description
Tempocol® is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine.
Intervention Type
Drug
Intervention Name(s)
Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)
Other Intervention Name(s)
Tempocol® (CBG-rvg number 109856)
Intervention Description
Peppermint oil capsule available as an over the counter prescription drug on the Dutch market.
Intervention Type
Drug
Intervention Name(s)
Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)
Other Intervention Name(s)
Tempocol-ColoPulse®
Intervention Description
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.
Primary Outcome Measure Information:
Title
T-max
Description
Time to reach maximum menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) concentration in plasma
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
C-max
Description
Menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) peak plasma concentrations
Time Frame
24 hours
Title
T-lag
Description
Time until a measurable plasma concentration of menthol-glucuronide occurs after oral administration of peppermint oil (45ug/L)
Time Frame
24 hours
Title
AUC
Description
Area under the plasma concentration-time curve from t=0 hrs until t=24 hrs.
Time Frame
24 hours
Title
T1/2
Description
elimination half-life; time required for the plasma concentration of menthol-glucuronide to reach half of its original value.
Time Frame
24 hours
Title
Menthol-glucuronide Urine Exretion Time Curve
Time Frame
24 hours
Title
L-Menthol Concentration in Feces
Time Frame
+/- 24 hours
Title
Difference in Total Number of Side Effects Per Time Point.
Time Frame
24 hours
Title
Tolerability Assessed by Heart Rate, Blood Pressure and Reported Side Effects
Description
Assessed by heart rate, blood pressure and reported side effects.
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A Masclee, Prof, PhD, MD
Organizational Affiliation
Maastricht University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maastricht University Medical Center
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
5800
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
24096020
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.
Results Reference
background
PubMed Identifier
20621586
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.
Results Reference
background
PubMed Identifier
24100754
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.
Results Reference
background
PubMed Identifier
21833945
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.
Results Reference
background
PubMed Identifier
30284674
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.
Results Reference
result

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

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