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

NCT ID: NCT02716285

Last Updated: 2018-11-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-17
• Study Completion Date: 2018-10-01

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.

Conditions

Irritable Bowel Syndrome; Abdominal Pain; Colonic Diseases, Functional

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ileocolonic release peppermint oil

Colon-targeted-delivery capsule containing 182mg of Peppermint Oil, to be taken orally, 3 times daily for 8 weeks (first week, dosing will be titred).

Group Type: EXPERIMENTAL

Ileocolonic release peppermint oil

Intervention Type: DRUG

Peppermint oil, menthae piperitae aetheroleum

Small intestinal release peppermint oil (Tempocol®)

Enteric-coated capsule containing 182mg of Peppermint Oil that release the oil in the small intestine, to be taken orally, 3 times daily for 8 weeks (first week, dosing will be titred).

Group Type: EXPERIMENTAL

Small intestinal release peppermint oil

Intervention Type: DRUG

Peppermint oil, menthae piperitae aetheroleum

Placebo

Capsule containing microcrystalline cellulose, to be taken orally, 3 times daily for 8 weeks (first week, dosing will be titred).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule, containing microcrystalline cellulose

Interventions

Ileocolonic release peppermint oil

Peppermint oil, menthae piperitae aetheroleum

Intervention Type: DRUG

Placebo

Placebo capsule, containing microcrystalline cellulose

Intervention Type: DRUG

Small intestinal release peppermint oil

Peppermint oil, menthae piperitae aetheroleum

Intervention Type: DRUG

Other Intervention Names

Tempocol

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

A Masclee, Prof., PhD., MD.

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Gelderse Vallei Hospital

Ede, Gelderland, Netherlands

Medical Center Leeuwarden

Leeuwarden, Provincie Friesland, Netherlands

Alrijne Hospital

Leiden, South Holland, Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Countries

Netherlands

References

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Reference Type: BACKGROUND

PMID: 20621586 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 24100754 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21389791 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19008265 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30284674 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34468079 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31470006 (View on PubMed)

Other Identifiers

2015-005467-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL56000.068.16; METC162009

Identifier Type: -

Identifier Source: org_study_id