The DOMINO Trial: Diet Or Medication in Irritable Bowel syNdrOme

Study Overview
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Brief Summary
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A randomized controlled trial to evaluate the short-term efficacy and long-term health economic impact of a dietary intervention compared to pharmacotherapy with a musculotropic spasmolytic agent for newly diagnosed or newly treated irritable bowel syndrome in primary care.

Detailed Description
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A randomized controlled trial (Phase IV trial) to evaluate the short-term efficacy and long-term health economic impact of a dietary intervention compared to pharmacotherapy with a musculotropic spasmolytic (otilonium bromide) agent for 470 newly diagnosed or newly treated irritable bowel syndrome patients in primary care. The primary objective of this trial is to study treatment efficacy (IBS-SSS responder rate) with diet versus medication after 8 weeks of therapy. The secondary endpoint is to study the quality of life and health economic impact over six months after the start of the initial treatment with diet versus medication. Finally, patient satisfaction during and after the different treatment modalities, HRU and WPAI-IBS score in subgroups according to IBS stool pattern subtype, faecal microbiota and serotonin synthesis genetic polymorphisms will also be investigated

Official Title
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A Randomized Controlled Trial to Evaluate the Short-term Efficacy and Long-term Health Economic Impact of a Dietary Intervention Compared to Pharmacotherapy With a Musculotropic Spasmolytic Agent for Newly Diagnosed or Newly Treated Irritable Bowel Syndrome in Primary Care

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Other: IBS Diet
* Drug: Otilonium Bromide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients are those of either gender, above the age of 18, eligible to give informed consent. Newly diagnosed with or newly to be treated for IBS in primary care, as this is the setting where the majority of these patients is managed. The diagnostic gold standard, in line with clinical practice, will be clinician's diagnostic judgment. Supportive information for the diagnosis of IBS will be provided to the GPs at the initial investigators meeting. This includes: a guidance for diagnosis and potentially useful additional tests based on the Rome IV management algorithm, a Rome IV-based diagnostic questionnaire with pictograms and a list of alarm symptoms. Patients who did not receive treatment over the preceding 3 months, and who did not receive long-term treatment (>3 consecutive weeks) with otilonium bromide in the past are eligible for the trial. Exclusion Criteria: Patients not capable to understand or be compliant with the study. Patients with concurrent organic gastrointestinal disease (inflammatory bowel disease), a history of major bowel surgery (not including minimal invasive surgery such as appendectomy or cholecystectomy, but including sigmoidectomy, hemicolectomy and small bowel resections) Patients who received treatment with otilonium bromide in the past for more than 3 weeks consecutively or who received otilonium bromide recently for any duration in the last 3 months. Patients who have used FODMAP or NICE diet before. Patients who recently (last 3 weeks) used other medication for IBS, or who changed their diet for IBS or for any other reason over the last 3 months. To be included in the trial patients should stop these treatments following the advice of their GP (see paragraph 8.9). Patients with diabetes, uncontrolled thyroid disease, active malignant disease (not including patients with cancer free diagnosis for more than 5 years), symptomatic uncontrolled endometriosis. Patients with a major psychiatric disease. The use of a single antidepressant on a stable dose for at least 3 months is allowed (see paragraph 8.9). Patients with drug abuse and/or alcohol abuse. Patients on pharmacologically prepared probiotic formulations (i.e. bought in the pharmacy) will be excluded. The use of probiotic drinks or yoghurts available from food stores, such as Activia®, Yakult ®, Actimel ®, is allowed but should be registered as complementary treatment(see paragraph 8.9). Women with active pregnancy plans in the coming 6 months are not eligible and women of childbearing potential are only eligible if they use effective contraception throughout the study. Also excluded are women of childbearing potential not using effective contraception or women planning to become pregnant the next 6 months (see paragraph 8.9). Methods of contraception considered highly effective are: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, a vasectomized partner or sexual abstinence (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf)

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Randomized Parallel study: diet vs medication (otilonium bromide)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBS diet<br>The simple IBS diet is a diet based on the Low FODMAPs diet and the NICE (National Institute of Health and Care Excellence) IBS diet. Patients will be aid to follow the diet with a mobile app. | Other: IBS Diet<br>* Patients will be randomized to a diet or a mediation treatment<br>|
| Active Comparator: Otilonium bromide<br>Otilonium bromide is a a frequently used musculotropic spasmolytic. The dosis used will be 40 mg t.i.d. | Drug: Otilonium Bromide<br>* Patients will be randomized to a diet or a mediation treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment efficacy of symptom severity | IBS-SSS: IBS symptom severity score The maximum achievable score is 500. Mild, moderate and severe cases were indicated by scores of 75 to 175, 175 to 300 and >300 respectively. Controls scored below 75 and patients scoring in this range can be considered to be in remission. Efficacy of treatment will be assess by calculating the proportion of patients in each arm with a drop of 50 points or more on the IBS-SSS. The higher the drop, the more the patient has improved. | 1.5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment efficacy in quality of life | Assessment will be done with the IBS-QoL questionnaires before and during the study. This includes IBS generic functional status and well-being, perceived quality of life specific to IBS, and work disability. Quality of life and health economic impact over 6 months after the start of the initial treatment with diet versus medication will be studied. Questionnaire includes a 5-point Likert response scale: not at all, slightly, moderately, quite a bit, and extremely or a great deal. All items were sum-scored to calculate total scores. | 1.5 year |