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

Florencia Carbone, Karen Van den Houte, Linde Besard, Céline Tack, Joris Arts, Philip Caenepeel, Hubert Piessevaux, Alain Vandenberghe, Christophe Matthys, Jessica Biesiekierski, Luc Capiau, Steven Ceulemans, Olivier Gernay, Lydia Jones, Sophie Maes, Christian Peetermans, Willem Raat, Jeroen Stubbe, Rudy Van Boxstael, Olivia Vandeput, Sophie Van Steenbergen, Lukas Van Oudenhove, Tim Vanuytsel, Michael Jones, Jan Tack, DOMINO Study Collaborators, Domino Study Collaborators, Alain Goorden, Alegonda Snijkers, An Leys, Annemiek Roelofs, Bart Schoolmeesters, Bart Vander Putten, Benjamin Van den Broek, Birgitta Baade-Joret, Céline Huberlant, Christian Peetermans, David Van Humbeek, Dirk Van den Brande, Dirk Wyseyr, Els Lemmens, Ethel Brits, Guido Simons, Hans Baetens, Hendrika Van Overmeire, Hilde Tack, Ilse Cupers, Ive Talboom, Jeroen Stubbe, Jonas Docx, Judith Deseins, Julie Biot, Julie Vancaillie, Kara Vandeloo, Karlijn Louwies, Karolien De Ceulaer, Karolien Lemmens, Katrien Scheers, Leen Verleure, Lies De Sutter, Lies Plancke, Liesbet Bruyninckx, Liesbeth Vanzeir, Lieve Vandersmisse, Linde Wyseur, Lode Vermeersch, Lodewijk Pas, Lore De Greef, Luc Capiau, Luc Van Braeckel, Lut De Groote, Lydia Jones, Maria Groot, Marianne Busschots, Marie-Hélène Landenne, Marieke Monstrey, Marie-Magdalena Haemels, Marleen Snellings, Maura Sisk, Nathalie Van de Vyver, Nikea Sannen, Olivia Vandeput, Olivier Gernay, Philippe Thoné, Phouthalack Narongsack, Pierre Vrins, Pieterjan Geusens, Rik Sauwens, Rudy Van Boxstael, Sigrid Musch, Sigrid Nous, Sofie Mazereel, Sophie Maes, Sophie Van Steenbergen, Stéphanie Biot, Steven Ceulemans, Stijn Geeraert, Tine Caeyers, Vincent Vanbelle, Willem Raat, Florencia Carbone, Karen Van den Houte, Linde Besard, Céline Tack, Joris Arts, Philip Caenepeel, Hubert Piessevaux, Alain Vandenberghe, Christophe Matthys, Jessica Biesiekierski, Luc Capiau, Steven Ceulemans, Olivier Gernay, Lydia Jones, Sophie Maes, Christian Peetermans, Willem Raat, Jeroen Stubbe, Rudy Van Boxstael, Olivia Vandeput, Sophie Van Steenbergen, Lukas Van Oudenhove, Tim Vanuytsel, Michael Jones, Jan Tack, DOMINO Study Collaborators, Domino Study Collaborators, Alain Goorden, Alegonda Snijkers, An Leys, Annemiek Roelofs, Bart Schoolmeesters, Bart Vander Putten, Benjamin Van den Broek, Birgitta Baade-Joret, Céline Huberlant, Christian Peetermans, David Van Humbeek, Dirk Van den Brande, Dirk Wyseyr, Els Lemmens, Ethel Brits, Guido Simons, Hans Baetens, Hendrika Van Overmeire, Hilde Tack, Ilse Cupers, Ive Talboom, Jeroen Stubbe, Jonas Docx, Judith Deseins, Julie Biot, Julie Vancaillie, Kara Vandeloo, Karlijn Louwies, Karolien De Ceulaer, Karolien Lemmens, Katrien Scheers, Leen Verleure, Lies De Sutter, Lies Plancke, Liesbet Bruyninckx, Liesbeth Vanzeir, Lieve Vandersmisse, Linde Wyseur, Lode Vermeersch, Lodewijk Pas, Lore De Greef, Luc Capiau, Luc Van Braeckel, Lut De Groote, Lydia Jones, Maria Groot, Marianne Busschots, Marie-Hélène Landenne, Marieke Monstrey, Marie-Magdalena Haemels, Marleen Snellings, Maura Sisk, Nathalie Van de Vyver, Nikea Sannen, Olivia Vandeput, Olivier Gernay, Philippe Thoné, Phouthalack Narongsack, Pierre Vrins, Pieterjan Geusens, Rik Sauwens, Rudy Van Boxstael, Sigrid Musch, Sigrid Nous, Sofie Mazereel, Sophie Maes, Sophie Van Steenbergen, Stéphanie Biot, Steven Ceulemans, Stijn Geeraert, Tine Caeyers, Vincent Vanbelle, Willem Raat

Abstract

Background: In Europe, IBS is commonly treated with musculotropic spasmolytics (eg, otilonium bromide, OB). In tertiary care, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet provides significant improvement. Yet, dietary treatment remains to be explored in primary care. We evaluated the effect of a smartphone FODMAP-lowering diet application versus OB on symptoms in primary care IBS.

Methods: IBS patients, recruited by primary care physicians, were randomised to 8 weeks of OB (40 mg three times a day) or diet and followed for 24 weeks. We compared IBS Symptom Severity Score and the proportion of responders (improvement ≥50 points) in all patients and the subgroup fulfilling Rome IV criteria (Rome+). We also evaluated treatment efficacy, quality of life, anxiety, depression, somatic symptom severity (Patient Health Questionnaire (PHQ15, PHQ9)) and treatment adherence and analysed predictors of response.

Results: 459 primary care IBS patients (41±15 years, 76% female, 70% Rome+) were randomised. The responder rate after 8 weeks was significantly higher with diet compared with OB (71% (155/218) vs 61% (133/217), p=0.03) and more pronounced in Rome+ (77% (118/153) vs 62% (98/158), p=0.004). Patients allocated to diet (199/212) were 94% adherent compared with 73% with OB (148/202) (p<0.001). The significantly higher response rate with diet was already observed after 4 weeks (62% (132/213) vs 51% (110/215), p=0.02) and a high symptom response persisted during follow-up. Predictors of response were female gender (OR=2.08, p=0.04) for diet and PHQ15 (OR=1.10, p=0.02) for OB.

Conclusion: In primary care IBS patients, a FODMAP-lowering diet application was superior to a spasmolytic agent in improving IBS symptoms. A FODMAP-lowering diet should be considered the first-line treatment for IBS in primary care.

Trial registration number: NCT04270487.

Keywords: IRRITABLE BOWEL SYNDROME; PRIMARY CARE; QUALITY OF LIFE.

Conflict of interest statement

Competing interests: JT has given Scientific advice to Alfa Wassermann, Allergan, Christian Hansen, Danone, Grünenthal, Ironwood, Janssen, Kiowa Kirin, Menarini, Mylan, Neutec, Novartis, Noventure, Nutricia, Shionogi, Shire, Takeda, Theravance, Tramedico, Truvion, Tsumura, Zealand and Zeria Pharmaceuticals, has received research support from Shire, Sofar and Tsumura, and has served on the Speaker Bureau for Abbott, Allergan, AstraZeneca, Janssen, Kyowa Kirin, Menarini, Mylan, Novartis, Shire, Takeda, Truvion and Zeria. Funding was provided by a Methusalem grant from Leuven University to JT. HP has given scientific advice to Allergan, Danone, Menarini, Merck Serono, Shire and Zeria and has served on the speaker Bureau of Menarini, Merck Serono, Shire and Zeria. LVO has given scientific advice to Danone and received research support from Nestlé. TV has given scientific advice to VectivBio, Shire, Dr. Falk Pharma, Takeda and Baxter; has received research support from Danone, MyHealth and VectivBio; and has served on the Speaker Bureau for Abbott, Tramedico, Truvion, Will Pharma, My Health, Kyowa Kirin, Menarini, Biocodex, Remedus, Fresenius Kabi and Dr. Falk Pharma. CM has served on the Speaker Bureau for Coca-Cola and Zespri and received travel/conference grants from Danone, Nestlé Health Sciences, Fresenius Kabi. This study was supported by a research grant from the Belgian Health Care Knowledge Centre (KCE). Questionnaires in this trial were developed, translated and provided by the Rome Foundation Research Institute.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials (CONSORT) diagram.
Figure 2
Figure 2
Responder rate was significantly higher in the diet group compared with medication after 4 (p=0.02) and 8 weeks (p=0.03) and more pronounced in Rome+ patients (p=0.004) based on Pearson χ2 test. OB, otilonium bromide; t.i.d., three times a day.
Figure 3
Figure 3
Change (±SE) in IBS-SSS at start, after 4 (p=0.007) and 8 weeks (p=0.049) of treatment based on mixed-model analysis. IBS-SSS, IBS Symptom Severity Scale; OB, otilonium bromide; t.i.d., three times a day.

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