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

Maastricht University Medical Centre (MUMC)

Status and phase: Completed; Phase 3

Conditions: Irritable Bowel Syndrome; Colonic Diseases, Functional; Abdominal Pain

Treatments: Drug: Placebo; Drug: Ileocolonic release peppermint oil; Drug: Small intestinal release peppermint oil

Study type: Interventional

Funder types: Other

Identifiers

NCT02716285

2015-005467-16 (EudraCT Number)

NL56000.068.16 METC162009;

Details and patient eligibility

About

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.

Enrollment: 190 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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190 participants in 3 patient groups, including a placebo group

Ileocolonic release peppermint oil

Experimental group

Description:

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).

Treatment:

Drug: Ileocolonic release peppermint oil

Small intestinal release peppermint oil (Tempocol®)

Experimental group

Description:

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).

Treatment:

Drug: Small intestinal release peppermint oil

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo