The DOMINO Trial: Diet Or Medication in Irritable Bowel syNdrOme (DOMINO)

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

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Other: IBS Diet; Drug: Otilonium Bromide

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 472
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Univeristy Hospital Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IBS diet; 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; Patients will be randomized to a diet or a mediation treatment
Active Comparator: Otilonium bromide; Otilonium bromide is a a frequently used musculotropic spasmolytic. The dosis used will be 40 mg t.i.d.	Drug: Otilonium Bromide; Patients will be randomized to a diet or a mediation treatment

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life in IBS	Euro-Qol quesrionnaire. This questionnaire includes 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. Additionallty, a VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. All the scores are taken into account.	1.5 year
Work Productivity and Activity Impairment in IBS	Work Productivity and Activity Impairment Questionnaire (WPAI) Levels of work productivity will be assess before and after treatment. The change of work productivity levels before and after treatment will be studied. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes, as follows: Questions: = currently employed; = hours missed due to health problems; = hours missed other reasons; = hours actually worked; = degree health affected productivity while working; = degree health affected regular activities Scores: Multiply scores by 100 to express in percentages. Percent work time missed due to health: Q2/(Q2+Q4) Percent impairment while working due to health: Q5/10 Percent overall work impairment due to health: Q2/(Q2+Q4)+[(1-(Q2/(Q2+Q4)))x(Q5/10)] Percent activity impairment due to health: Q6/10	1.5 year
Depression levels in IBS	PHQ: patient health questionnaire This is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of -not at all,‖ -several days,‖ -more than half the days,‖ and -nearly every day,‖ respectively. PHQ-9 total score (sum) for the nine items ranges from 0 to 27. Scores represent: 0-5 = mild 6-10 = moderate 11-15 = moderately severe 16-20 = severe depression Levels of depression will be assess before and after treatment. The change of depression levels before and after treatment will be studied.	1.5 year
Somatic levels in IBS	PHQ: patient health questionnaire This is calculated by assigning scores of 0, 1, and 2 to the response categories of -not at all‖, -bothered a little‖, and -bothered a lot‖, for the 13 somatic symptoms and 2 items from the depression module (sleep and tired) are scored 0 (-not at all‖), 1 (-several days‖) or 2 (-more than half the days‖ or -nearly every day‖). PHQ-15 scores (sum of scores) of 5, 10, and 15 represent cutpoints for low, medium, and high somatic symptom severity, respectively. Levels of somatization will be assess before and after treatment. The change of somatization levels before and after treatment will be studied.	1.5
Anxiety levels in IBS	GAD-7 - patient health questionnaire This is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of "not at all," "several days," "more than half the days," and "nearly every day," respectively. GAD-7 total score for the seven items ranges from 0 to 21. When screening for anxiety disorders, a recommended cutpoint for further evaluation is a score of 10 or greater.	1.5 years
Health resourse utilisation in IBS	Health resourse utilisation in IBS with the HRU questionnaire. Both direct and indirect health costs, including self-costs to patients, will be compared at the different time points (2,4,6 months). They will also be compared to the (retrospective) cost assessment at baseline. The total direct costs of the utilization of healthcare resources associated with IBS will be calculated in terms of (additional) primary care visits, secondary care visits, hospitalizations, diagnostic tests and procedures, prescription and non-prescription medication and complementary therapies.	1.5 years
Genetic prediction to treatment in IBS	Exploratory outcome GWAS analysis of IBS genetics. Pathophysiological and treatment predictors will be investigated in an exploratory setting	1.5 years
Microbiome prediction to treatment in IBS	Exploratory outcome Microbiome analysis of IBS stool samples. Pathophysiological and treatment predictors will be investigated in an exploratory setting	1.5 years

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Carbone F, Van den Houte K, Besard L, Tack C, Arts J, Caenepeel P, Piessevaux H, Vandenberghe A, Matthys C, Biesiekierski J, Capiau L, Ceulemans S, Gernay O, Jones L, Maes S, Peetermans C, Raat W, Stubbe J, Van Boxstael R, Vandeput O, Van Steenbergen S, Van Oudenhove L, Vanuytsel T, Jones M, Tack J; DOMINO Study Collaborators; Domino Study Collaborators. Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute. Gut. 2022 Nov;71(11):2226-2232. doi: 10.1136/gutjnl-2021-325821. Epub 2022 Apr 28.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Actual): May 4, 2020
• Study Completion (Actual): July 6, 2020

Study Registration Dates

• First Submitted: September 27, 2019
• First Submitted That Met QC Criteria: February 13, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Gastrointestinal Agents; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Bromides; Octylonium
• Other Study ID Numbers: S59482

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No