Peppermint Oil for the Treatment of Irritable Bowel Syndrome: Optimizing Therapeutic Strategies Using Targeted Delivery

Irritable Bowel Syndrome Clinical Trial

— PERSUADE  

Official title:

Peppermint Oil for the Treatment of Irritable Bowel Syndrome: Optimizing Therapeutic Strategies Using Targeted Delivery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02716285
• Other study ID #: NL56000.068.16; METC162009
• Secondary ID: 2015-005467-16
• Status: Completed
• Phase: Phase 3
• Start date: August 17, 2016
• Est. completion date: October 1, 2018

Study information

• Verified date: October 2018
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: October 1, 2018
• Est. primary completion date: May 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Abdominal Pain
• Colonic Diseases
• Colonic Diseases, Functional
• Irritable Bowel Syndrome
• Syndrome

Intervention

Drug:
• Ileocolonic release peppermint oil
Peppermint oil, menthae piperitae aetheroleum
• Placebo
Placebo capsule, containing microcrystalline cellulose
• Small intestinal release peppermint oil
Peppermint oil, menthae piperitae aetheroleum

Locations

Country	Name	City	State
Netherlands	Gelderse Vallei Hospital	Ede	Gelderland
Netherlands	Medical Center Leeuwarden	Leeuwarden	Friesland
Netherlands	Alrijne Hospital	Leiden	Zuid Holland
Netherlands	Maastricht University Medical Center	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

References & Publications (6)

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. Review. — View 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. Review. Erratum in: BMJ.2009;338:b1881. — View 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. Review. — View 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. — View 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. — View 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 Oct 4. doi: 10.1007/s12325-018-0802-1. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Abdominal pain response rate after 8 weeks of treatment	A responder is defined as a patient who experiences at least a 30 percent decrease in the weekly average of worst daily abdominal pain (measured daily, on an 11 point NRS) compared to baseline weekly average in at least 50 percent of the weeks in which the treatment in given.	8 weeks
Primary	Degree of relief response rate after 8 weeks of treatment.	A responder is defined as a patient who experiences a weekly relief of 1 or 2 (on a 7 point NRS) in at least 50 percent of the weeks in which treatment is given.	8 weeks
Secondary	Global symptom improvement	As determined by IBS-SSS (IBS symptom severity scale)	8 weeks
Secondary	Abdominal Discomfort	As determined by symptom diary	8 weeks
Secondary	Bloating	As determined by IBS-SSS (IBS - symptom severity scale)	8 weeks
Secondary	Regurgitation	As determined by symptom diary	8 weeks
Secondary	Nausea	As determined by symptom diary	8 weeks
Secondary	Urgency	As determined by symptom diary	8 weeks
Secondary	Abdominal cramps	As determined by symptom diary	8 weeks
Secondary	Average stool frequency and consistency	Measured by bristol stool chart	8 weeks
Secondary	Indirect costs	Determined by Production Cost Questionnaire (PCQ) questionnaire	8 weeks, 3 and 6 months
Secondary	Direct costs	Determined by Medical Cost Questionnaire (MCQ) questionnaire	8 weeks, 3 and 6 months
Secondary	General Quality of Life	As determined by Euro-Qol-5D (EQ-5D)	8 weeks, 3 and 6 months
Secondary	IBS related Quality of Life	As determined by IBS-Quality of life questionnaire (IBS-QoL)	8 weeks, 3 and 6 months
Secondary	Use of Over the counter medication and rescue medication	Number of drugs taken as rescue medication (This is not an intervention)	8 weeks
Secondary	Number and severity of side effects	Determined by daily diary	8 weeks
Secondary	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);		3 and 6 months after discontinuation of treatment
Secondary	Responder rates when missing are interpreted as "no effect"		8 weeks