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

doi:10.1136/gutjnl-2021-325821

Randomized Controlled Trial

. 2022 Nov;71(11):2226-2232.

doi: 10.1136/gutjnl-2021-325821. Epub 2022 Apr 28.

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^{1

2}, Karen Van den Houte², Linde Besard¹, Céline Tack¹, Joris Arts^{1

3}, Philip Caenepeel^{1

3}, Hubert Piessevaux⁴, Alain Vandenberghe⁵, Christophe Matthys⁶, Jessica Biesiekierski^{2

7}, Luc Capiau⁸, Steven Ceulemans⁸, Olivier Gernay⁸, Lydia Jones⁸, Sophie Maes⁸, Christian Peetermans⁸, Willem Raat⁹, Jeroen Stubbe⁸, Rudy Van Boxstael⁸, Olivia Vandeput⁸, Sophie Van Steenbergen⁸, Lukas Van Oudenhove², Tim Vanuytsel^{1

2}, Michael Jones¹⁰, Jan Tack^{11

2

12

13}; DOMINO Study Collaborators; Domino Study Collaborators

Collaborators, Affiliations

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

Affiliations

¹ Department of Gastroenterology, KU Leuven University Hospitals Leuven, Leuven, Belgium.
² TARGID (Translational Research Center for Gastrointestinal Disorders), KU Leuven, Leuven, Belgium.
³ Gastroenterology, Ziekenhuis Oost-Limburg, Genk, Belgium.
⁴ Department of Gastroenterology and Hepatology, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
⁵ Medical Research Laboratories International, Chaumont-Gistoux, Belgium.
⁶ Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
⁷ Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Victoria, Australia.
⁸ Primary care physician, Domino primary care physician study group, Leuven, Belgium.
⁹ Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium.
¹⁰ Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
¹¹ Department of Gastroenterology, KU Leuven University Hospitals Leuven, Leuven, Belgium jan.tack@med.kuleuven.ac.be.
¹² Rome Foundation Research Institute, Raleigh, North Carolina, USA.
¹³ Rome Foundation, Raleigh, North Carolina, USA.

PMID: 35483886
PMCID: PMC9554021
DOI: 10.1136/gutjnl-2021-325821

Randomized Controlled Trial

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 et al. Gut. 2022 Nov.

. 2022 Nov;71(11):2226-2232.

doi: 10.1136/gutjnl-2021-325821. Epub 2022 Apr 28.

Authors

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

Affiliations

¹ Department of Gastroenterology, KU Leuven University Hospitals Leuven, Leuven, Belgium.
² TARGID (Translational Research Center for Gastrointestinal Disorders), KU Leuven, Leuven, Belgium.
³ Gastroenterology, Ziekenhuis Oost-Limburg, Genk, Belgium.
⁴ Department of Gastroenterology and Hepatology, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
⁵ Medical Research Laboratories International, Chaumont-Gistoux, Belgium.
⁶ Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
⁷ Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Victoria, Australia.
⁸ Primary care physician, Domino primary care physician study group, Leuven, Belgium.
⁹ Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium.
¹⁰ Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
¹¹ Department of Gastroenterology, KU Leuven University Hospitals Leuven, Leuven, Belgium jan.tack@med.kuleuven.ac.be.
¹² Rome Foundation Research Institute, Raleigh, North Carolina, USA.
¹³ Rome Foundation, Raleigh, North Carolina, USA.

PMID: 35483886
PMCID: PMC9554021
DOI: 10.1136/gutjnl-2021-325821

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.

PubMed Disclaimer

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.

Figures

**Figure 1**
Consolidated Standards of Reporting Trials (CONSORT) diagram.

**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**
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.

See this image and copyright information in PMC

Comment in

Further research needed to determine first-line therapy for IBS in primary care.
Rej A, Sanders DS, Aziz I. Rej A, et al. Gut. 2023 May;72(5):1024-1025. doi: 10.1136/gutjnl-2022-328047. Epub 2022 Jun 22. Gut. 2023. PMID: 35732423 No abstract available.
In IBS, a smartphone application for self-managing a FODMAP-lowering diet vs. otilonium bromide reduced symptoms at 8 wk.
Cox JF 3rd. Cox JF 3rd. Ann Intern Med. 2022 Aug;175(8):JC91. doi: 10.7326/J22-0059. Epub 2022 Aug 2. Ann Intern Med. 2022. PMID: 35914257

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DOMINO trial post hoc analysis: evaluation of the diet effects on symptoms in IBS subtypes.
Di Rosa C, Van den Houte K, Altomare A, Guarino MPL, Besard L, Arts J, Caenepeel P, Piessevaux H, Vandenberghe A, Matthys C, Biesiekierski JR, 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, Carbone F. Di Rosa C, et al. Therap Adv Gastroenterol. 2024 Jul 30;17:17562848241255296. doi: 10.1177/17562848241255296. eCollection 2024. Therap Adv Gastroenterol. 2024. PMID: 39086991 Free PMC article.
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References

1. Drossman DA. Functional gastrointestinal disorders: what's new for Rome IV? Lancet Gastroenterol Hepatol 2016;1:6–8. 10.1016/S2468-1253(16)30022-X - DOI - PubMed
1. Sperber AD, Bangdiwala SI, Drossman DA, et al. . Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation global study. Gastroenterology 2021;160:99–114. 10.1053/j.gastro.2020.04.014 - DOI - PubMed
1. Van den Houte K, Carbone F, Pannemans J, et al. . Prevalence and impact of self-reported irritable bowel symptoms in the general population. United European Gastroenterol J 2019;7:307–15. 10.1177/2050640618821804 - DOI - PMC - PubMed
1. Tack J, Stanghellini V, Mearin F, et al. . Economic burden of moderate to severe irritable bowel syndrome with constipation in six European countries. BMC Gastroenterol 2019;19:69. 10.1186/s12876-019-0985-1 - DOI - PMC - PubMed
1. Canavan C, West J, Card T. Review article: the economic impact of the irritable bowel syndrome. Aliment Pharmacol Ther 2014;40:1023–34. 10.1111/apt.12938 - DOI - PubMed

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[1] Drossman DA. Functional gastrointestinal disorders: what's new for Rome IV? Lancet Gastroenterol Hepatol 2016;1:6–8. 10.1016/S2468-1253(16)30022-X - DOI - PubMed

[2] Drossman DA. Functional gastrointestinal disorders: what's new for Rome IV? Lancet Gastroenterol Hepatol 2016;1:6–8. 10.1016/S2468-1253(16)30022-X - DOI - PubMed

[3] Sperber AD, Bangdiwala SI, Drossman DA, et al. . Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation global study. Gastroenterology 2021;160:99–114. 10.1053/j.gastro.2020.04.014 - DOI - PubMed

[4] Sperber AD, Bangdiwala SI, Drossman DA, et al. . Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation global study. Gastroenterology 2021;160:99–114. 10.1053/j.gastro.2020.04.014 - DOI - PubMed

[5] Van den Houte K, Carbone F, Pannemans J, et al. . Prevalence and impact of self-reported irritable bowel symptoms in the general population. United European Gastroenterol J 2019;7:307–15. 10.1177/2050640618821804 - DOI - PMC - PubMed

[6] Van den Houte K, Carbone F, Pannemans J, et al. . Prevalence and impact of self-reported irritable bowel symptoms in the general population. United European Gastroenterol J 2019;7:307–15. 10.1177/2050640618821804 - DOI - PMC - PubMed

[7] Tack J, Stanghellini V, Mearin F, et al. . Economic burden of moderate to severe irritable bowel syndrome with constipation in six European countries. BMC Gastroenterol 2019;19:69. 10.1186/s12876-019-0985-1 - DOI - PMC - PubMed

[8] Tack J, Stanghellini V, Mearin F, et al. . Economic burden of moderate to severe irritable bowel syndrome with constipation in six European countries. BMC Gastroenterol 2019;19:69. 10.1186/s12876-019-0985-1 - DOI - PMC - PubMed

[9] Canavan C, West J, Card T. Review article: the economic impact of the irritable bowel syndrome. Aliment Pharmacol Ther 2014;40:1023–34. 10.1111/apt.12938 - DOI - PubMed

[10] Canavan C, West J, Card T. Review article: the economic impact of the irritable bowel syndrome. Aliment Pharmacol Ther 2014;40:1023–34. 10.1111/apt.12938 - DOI - PubMed

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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

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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

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