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

Study Overview
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Brief Summary
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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.

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

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

Intervention / Treatment
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* Drug: Ileocolonic release peppermint oil
* Drug: Placebo
* Drug: Small intestinal release peppermint oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: Insufficient fluency of the Dutch language; 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); 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ileocolonic release peppermint oil<br>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<br>* Peppermint oil, menthae piperitae aetheroleum<br>|
| Experimental: Small intestinal release peppermint oil (Tempocol®)<br>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<br>* Peppermint oil, menthae piperitae aetheroleum<br>* Other names: Tempocol;|
| Placebo Comparator: Placebo<br>Capsule containing microcrystalline cellulose, to be taken orally, 3 times daily for 8 weeks (first week, dosing will be titred). | Drug: Placebo<br>* Placebo capsule, containing microcrystalline cellulose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global symptom improvement | As determined by IBS-SSS (IBS symptom severity scale) | 8 weeks | 
| Abdominal Discomfort | As determined by symptom diary | 8 weeks | 
| Bloating | As determined by IBS-SSS (IBS - symptom severity scale) | 8 weeks | 
| Regurgitation | As determined by symptom diary | 8 weeks | 
| Nausea | As determined by symptom diary | 8 weeks | 
| Urgency | As determined by symptom diary | 8 weeks | 
| Abdominal cramps | As determined by symptom diary | 8 weeks | 
| Average stool frequency and consistency | Measured by bristol stool chart | 8 weeks | 
| Indirect costs | Determined by Production Cost Questionnaire (PCQ) questionnaire | 8 weeks, 3 and 6 months | 
| Direct costs | Determined by Medical Cost Questionnaire (MCQ) questionnaire | 8 weeks, 3 and 6 months | 
| General Quality of Life | As determined by Euro-Qol-5D (EQ-5D) | 8 weeks, 3 and 6 months | 
| IBS related Quality of Life | As determined by IBS-Quality of life questionnaire (IBS-QoL) | 8 weeks, 3 and 6 months | 
| Use of Over the counter medication and rescue medication | Number of drugs taken as rescue medication (This is not an intervention) | 8 weeks | 
| Number and severity of side effects | Determined by daily diary | 8 weeks | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irritable Bowel Syndrome, Abdominal pain, Targeted Delivery, Peppermint oil