Clinical trial NCT02716285: Peppermint Oil for the Treatment of Irritable Bowel Syndrome: Optimizing Therapeutic Strategies Using Targeted Delivery
Official title: Peppermint Oil for the Treatment of Irritable Bowel Syndrome: Optimizing Therapeutic Strategies Using Targeted Delivery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Irritable Bowel Syndrome
Abdominal Pain
Colonic Diseases, Functional
Keywords: Irritable Bowel Syndrome
Abdominal pain
Targeted Delivery
Peppermint oil
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2016-03-23
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Peppermint oil has shown to be effective in the treatment of Irritable Bowel Syndrome (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 will conduct a multicenter randomized, placebo controlled trial to investigate the effects of an eight-week peppermint oil treatment in IBS patients according to current European Medicines Agency (EMA) / US Food and Drug Administration (FDA) guidelines. To improve efficacy and to reduce side effects, the investigators aim to study the use of a new peppermint oil formulation, a colon-targeted-delivery capsule that will release the oil in the (ileo-) colonic region specifically.


Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 75 years;
2. Diagnosed with Irritable Bowel Syndrome according to the Rome IV criteria:

   (Recurrent abdominal pain, at least 1 day/week for the last 3 months; Symptom onset at least 6 months prior to diagnosis; Associated with two or more of the following:
   1. Pain related to defecation;
   2. Pain associated with a change in frequency of stool;
   3. Pain associated with a change in form (appearance/consistency) of stool
3. Based on the medical history and previous examination, no other causes for the abdominal complaints can be defined. Especially no history of:

   1. Inflammatory Bowel Disease;
   2. Celiac Disease;
   3. Thyroid dysfunction (if not well-regulated). If alarm symptoms (including unexplained rectal blood loss or weight loss) are present, a colonoscopy has been performed and was negative for other causes.
4. Women in fertile age (\<55 years old) must use contraception or be postmenopausal for at least two years.
5. Average worst abdominal pain score (on 11-point NRS) of \> 3, during the two-week run-in period.

Exclusion Criteria:

1. Insufficient fluency of the Dutch language;
2. Any previous use (also incidental use) of peppermint oil capsules in the last 3 months prior to inclusion (the use of peppermint tea, menthol candy etc. is allowed);
3. The inability to stop regular use of medication affecting the gastro-intestinal system (such as Non Steroidal Anti Inflammatory Drugs (NSAID), laxatives, prokinetics, opioids, smasmolytics and anti-diarrhoeal drugs). This use should be halted at least 1 week before enrollment into the run-in period;

   1. The use of 1 antidepressant drug is allowed, providing dosing has been stable for \> 6 weeks before enrollment;
   2. The use of 1 proton pump inhibitor (PPI) is allowed, providing dosing has been stable \> 6 weeks before enrollment;
4. Previous major abdominal surgery or radiotherapy interfering with gastrointestinal function:

   1. Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unless within the past 6 months;
   2. Other surgery upon judgment of the principle investigator;
5. History of liver disease, cholangitis, achlorhydria, gallstones or other diseases of the gallbladder/biliary system;
6. Pregnancy, lactation;
7. Using drugs of abuse;
8. Known allergic reaction to peppermint.

Primary outcomes:
measure: Abdominal pain response rate after 8 weeks of treatment
timeFrame: 8 weeks
measure: Degree of relief response rate after 8 weeks of treatment.
timeFrame: 8 weeks
Secondary outcomes:
measure: Global symptom improvement
timeFrame: 8 weeks
measure: Abdominal Discomfort
timeFrame: 8 weeks
measure: Bloating
timeFrame: 8 weeks
measure: Regurgitation
timeFrame: 8 weeks
measure: Nausea
timeFrame: 8 weeks
measure: Urgency
timeFrame: 8 weeks
measure: Abdominal cramps
timeFrame: 8 weeks
measure: Average stool frequency and consistency
timeFrame: 8 weeks
measure: Indirect costs
timeFrame: 8 weeks, 3 and 6 months
measure: Direct costs
timeFrame: 8 weeks, 3 and 6 months
measure: General Quality of Life
timeFrame: 8 weeks, 3 and 6 months
measure: IBS related Quality of Life
timeFrame: 8 weeks, 3 and 6 months
measure: Use of Over the counter medication and rescue medication
timeFrame: 8 weeks
measure: Number and severity of side effects
timeFrame: 8 weeks
measure: Responder rates following discontinuation of treatment at 3 and 6 months, different thresholds for the responder analysis of abdominal pain (e.g. 40 and 50 percent improvement);
timeFrame: 3 and 6 months after discontinuation of treatment
measure: Responder rates when missing are interpreted as "no effect"
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Leeuwarden
country: Netherlands
facility: Medical Center Leeuwarden
state: Friesland
city: Ede
country: Netherlands
facility: Gelderse Vallei Hospital
state: Gelderland
city: Leiden
country: Netherlands
facility: Alrijne Hospital
state: Zuid Holland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
Study officials:
affiliation: Maastricht University Medical Center
name: A Masclee, Prof., PhD., MD.
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: Enck P, Junne F, Klosterhalfen S, Zipfel S, Martens U. Therapy options in irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1402-11. doi: 10.1097/MEG.0b013e3283405a17.
citation: Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, Moayyedi P. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008 Nov 13;337:a2313. doi: 10.1136/bmj.a2313.
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.
citation: Weerts ZZRM, Essers BAB, Jonkers DMAE, Willems JIA, Janssen DJPA, Witteman BJM, Clemens CHM, Westendorp A, Masclee AAM, Keszthelyi D. A trial-based economic evaluation of peppermint oil for the treatment of irritable bowel syndrome. United European Gastroenterol J. 2021 Nov;9(9):997-1006. doi: 10.1002/ueg2.12134. Epub 2021 Sep 1.
citation: Weerts ZZRM, Masclee AAM, Witteman BJM, Clemens CHM, Winkens B, Brouwers JRBJ, Frijlink HW, Muris JWM, De Wit NJ, Essers BAB, Tack J, Snijkers JTW, Bours AMH, de Ruiter-van der Ploeg AS, Jonkers DMAE, Keszthelyi D. Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome. Gastroenterology. 2020 Jan;158(1):123-136. doi: 10.1053/j.gastro.2019.08.026. Epub 2019 Aug 27.