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

Phase 3

Completed

• Conditions: Irritable Bowel Syndrome; Colonic Diseases, Functional; Abdominal Pain
• Interventions: Drug: Placebo; Drug: Ileocolonic release peppermint oil; Drug: Small intestinal release peppermint oil

• Registration Number: NCT02716285
• Lead Sponsor: Maastricht University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-08
• Study First Submitted QC: 2016-03-22
• Study First Posted: 2016-03-23
• Study Start: 2016-08-17
• Primary Completion: 2018-05-01
• Status Verified: 2018-10
• Study Completion: 2018-10-01
• Last Update Submitted: 2018-10-31
• Last Update Posted: 2018-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 190

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Capsule containing microcrystalline cellulose, to be taken orally, 3 times daily for 8 weeks (first week, dosing will be titred).
Ileocolonic release peppermint oil	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).
Small intestinal release peppermint oil (Tempocol®)	Small intestinal release peppermint oil	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).

Primary Outcome Measures

Name	Time	Method
Degree of relief response rate after 8 weeks of treatment.	8 weeks	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.
Abdominal pain response rate after 8 weeks of treatment	8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Regurgitation	8 weeks	As determined by symptom diary
Use of Over the counter medication and rescue medication	8 weeks	Number of drugs taken as rescue medication (This is not an intervention)
Nausea	8 weeks	As determined by symptom diary
Abdominal Discomfort	8 weeks	As determined by symptom diary
Global symptom improvement	8 weeks	As determined by IBS-SSS (IBS symptom severity scale)
Urgency	8 weeks	As determined by symptom diary
Average stool frequency and consistency	8 weeks	Measured by bristol stool chart
Bloating	8 weeks	As determined by IBS-SSS (IBS - symptom severity scale)
Abdominal cramps	8 weeks	As determined by symptom diary
Indirect costs	8 weeks, 3 and 6 months	Determined by Production Cost Questionnaire (PCQ) questionnaire
Direct costs	8 weeks, 3 and 6 months	Determined by Medical Cost Questionnaire (MCQ) questionnaire
General Quality of Life	8 weeks, 3 and 6 months	As determined by Euro-Qol-5D (EQ-5D)
IBS related Quality of Life	8 weeks, 3 and 6 months	As determined by IBS-Quality of life questionnaire (IBS-QoL)
Number and severity of side effects	8 weeks	Determined by daily diary
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
Responder rates when missing are interpreted as "no effect"	8 weeks

Trial Locations

Locations (4)

Alrijne Hospital; 🇳🇱 Leiden, Zuid Holland, Netherlands

Maastricht University Medical Center; 🇳🇱 Maastricht, Netherlands

Medical Center Leeuwarden; 🇳🇱 Leeuwarden, Friesland, Netherlands

Gelderse Vallei Hospital; 🇳🇱 Ede, Gelderland, Netherlands