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

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 atleast 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

4. Based on the medical history and previous examination, no other causes for theabdominal complaints can be defined. Especially no history of:

5. Inflammatory Bowel Disease;

6. Celiac Disease;

7. Thyroid dysfunction (if not well-regulated). If alarm symptoms (includingunexplained rectal blood loss or weight loss) are present, a colonoscopy has beenperformed and was negative for other causes.

8. Women in fertile age (<55 years old) must use contraception or be postmenopausal forat least two years.

9. Average worst abdominal pain score (on 11-point NRS) of > 3, during the two-weekrun-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 monthsprior 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 1week before enrollment into the run-in period;

4. The use of 1 antidepressant drug is allowed, providing dosing has been stable for > 6 weeks before enrollment;

5. The use of 1 proton pump inhibitor (PPI) is allowed, providing dosing has beenstable > 6 weeks before enrollment;

6. Previous major abdominal surgery or radiotherapy interfering with gastrointestinalfunction:

7. Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unlesswithin the past 6 months;

8. Other surgery upon judgment of the principle investigator;

9. History of liver disease, cholangitis, achlorhydria, gallstones or other diseases ofthe gallbladder/biliary system;

10. Pregnancy, lactation;

11. Using drugs of abuse;

12. Known allergic reaction to peppermint.