Clinical trial NCT04270487: The DOMINO Trial: Diet Or Medication in Irritable Bowel syNdrOme
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Irritable Bowel Syndrome
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2020-02-17
Enrollment: 472
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Parallel study: diet vs medication (otilonium bromide)
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Treatment efficacy of symptom severity
timeFrame: 1.5 year
Secondary outcomes:
measure: Treatment efficacy in quality of life
timeFrame: 1.5 year
Other outcomes:
measure: Quality of life in IBS
timeFrame: 1.5 year
measure: Work Productivity and Activity Impairment in IBS
timeFrame: 1.5 year
measure: Depression levels in IBS
timeFrame: 1.5 year
measure: Somatic levels in IBS
timeFrame: 1.5
measure: Anxiety levels in IBS
timeFrame: 1.5 years
measure: Health resourse utilisation in IBS
timeFrame: 1.5 years
measure: Genetic prediction to treatment in IBS
timeFrame: 1.5 years
measure: Microbiome prediction to treatment in IBS
timeFrame: 1.5 years
Locations:
city: Leuven
country: Belgium
facility: Univeristy Hospital Leuven
state: Vlaams-Brabant
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Jan Tack, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.