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

NCT02716285 | Completed Phase 3

• 2 other identifiers: NL56000.068.16; METC1620092015-005467-16
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 4

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

Keywords

Irritable Bowel Syndrome; Abdominal pain; Targeted Delivery; Peppermint oil

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (16)

• Global symptom improvement

  8 weeks

• Abdominal Discomfort

  8 weeks

• Bloating

  8 weeks

• Regurgitation

  8 weeks

• Nausea

  8 weeks

Study Arms (3)

Ileocolonic release peppermint oil

EXPERIMENTAL

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).

Drug: Ileocolonic release peppermint oil

Small intestinal release peppermint oil (Tempocol®)

EXPERIMENTAL

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).

Drug: Small intestinal release peppermint oil

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Ileocolonic release peppermint oil DRUG

Peppermint oil, menthae piperitae aetheroleum

Ileocolonic release peppermint oil

Placebo DRUG

Placebo capsule, containing microcrystalline cellulose

Placebo

Small intestinal release peppermint oil DRUG

Peppermint oil, menthae piperitae aetheroleum

Also known as: Tempocol

Small intestinal release peppermint oil (Tempocol®)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years;
• 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:
• Pain related to defecation;
• Pain associated with a change in frequency of stool;
• Pain associated with a change in form (appearance/consistency) of stool
• Based on the medical history and previous examination, no other causes for the abdominal complaints can be defined. Especially no history of:
• Inflammatory Bowel Disease;
• Celiac Disease;
• 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.
• Women in fertile age (\<55 years old) must use contraception or be postmenopausal for at least two years.
• Average worst abdominal pain score (on 11-point NRS) of \> 3, during the two-week run-in period.

You may not qualify if:

• Insufficient fluency of the Dutch language;
• 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;
• The use of 1 antidepressant drug is allowed, providing dosing has been stable for \> 6 weeks before enrollment;
• The use of 1 proton pump inhibitor (PPI) is allowed, providing dosing has been stable \> 6 weeks before enrollment;
• Previous major abdominal surgery or radiotherapy interfering with gastrointestinal function:
• Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unless within the past 6 months;
• Other surgery upon judgment of the principle investigator;
• History of liver disease, cholangitis, achlorhydria, gallstones or other diseases of the gallbladder/biliary system;
• Pregnancy, lactation;
• Using drugs of abuse;
• Known allergic reaction to peppermint.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (4)

Gelderse Vallei Hospital

Ede, Gelderland, 6716 RP, Netherlands

Location

Medical Center Leeuwarden

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

Location

Alrijne Hospital

Leiden, South Holland, 2334 CK, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 ER, Netherlands

Location

Related Publications (8)

• 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.

  PMID: 20621586 BACKGROUND

• 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.

  PMID: 24096020 BACKGROUND

• 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.

  PMID: 24100754 BACKGROUND

• 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.

  PMID: 21389791 BACKGROUND

• 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.

  PMID: 19008265 BACKGROUND

• 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.

  PMID: 30284674 BACKGROUND

• 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.

  PMID: 34468079 DERIVED

• 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.

  PMID: 31470006 DERIVED

MeSH Terms

Conditions

Irritable Bowel Syndrome; Abdominal Pain; Colonic Diseases, Functional

Condition Hierarchy (Ancestors)

Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive

Study Officials

• A Masclee, Prof., PhD., MD.

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 23, 2016
• Study Start: August 17, 2016
• Primary Completion: May 1, 2018
• Study Completion: October 1, 2018
• Last Updated: November 2, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4)