Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis
Background The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world’s population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles...
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BMJ Publishing Group
2025-01-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/1/e088290.full |
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| author | Joanne Verheij Hilde Herrema Max Nieuwdorp Koen Wortelboer Aldo Grefhorst Quinten J. J. Augustijn Pleun de Groen Jos F ML Seegers Ismail Sahin Gül Peter Suenaert Willem M. de Vos Adriaan G. Holleboom |
| author_facet | Joanne Verheij Hilde Herrema Max Nieuwdorp Koen Wortelboer Aldo Grefhorst Quinten J. J. Augustijn Pleun de Groen Jos F ML Seegers Ismail Sahin Gül Peter Suenaert Willem M. de Vos Adriaan G. Holleboom |
| author_sort | Joanne Verheij |
| collection | DOAJ |
| description | Background The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world’s population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles, and several microbial components have been implicated in MASLD pathophysiology. Indeed, earlier studies demonstrated that hepatic necroinflammation was reduced in individuals with MASLD after allogenic faecal microbiota transplantation (FMT) from healthy donors on a vegan diet. Here, we further investigate the therapeutic potential of gut microbiome modulation using a syntrophic combination of next-generation beneficial bacteria with FMT in individuals with advanced MASLD.Methods and analysis This trial is a randomised, double-blind, placebo-controlled study investigating the therapeutic potential of lyophilised faecal microbiota capsules (LFMCs) in individuals with metabolic dysfunction-associated steatohepatitis. In this study, 48 participants will be randomised 1:1 to receive either healthy vegan donor LFMCs or placebo for 24 weeks. In addition, all participants will be supplemented with a set of next-generation beneficial bacteria, including Anaerobutyricum soehngenii, pasteurised Akkermansia muciniphila and Bifidobacterium animalis subsp. lactis, as well as fructo-oligosaccharides. A liver biopsy will be performed at baseline and at the end of the trial. In addition, participants will be assessed through MRI, FibroScan, blood tests, faecal samples and continuous glucose monitoring. The first participant was enrolled on 25 April 2023.Ethics and dissemination Ethical approval was obtained from the Medical Ethics Committee of the University Medical Centre of Amsterdam. The results of this study will be disseminated through peer-reviewed journals.Trial Registration number The trial is registered on clinicaltrials.gov (NCT05821010). |
| format | Article |
| id | doaj-art-3f459818480b4f94913590bbcf0a22ec |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-3f459818480b4f94913590bbcf0a22ec2025-01-10T06:25:10ZengBMJ Publishing GroupBMJ Open2044-60552025-01-0115110.1136/bmjopen-2024-088290Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitisJoanne Verheij0Hilde Herrema1Max Nieuwdorp2Koen Wortelboer3Aldo Grefhorst4Quinten J. J. Augustijn5Pleun de Groen6Jos F ML Seegers7Ismail Sahin Gül8Peter Suenaert9Willem M. de Vos10Adriaan G. Holleboom115 Pathology, AMC, Amsterdam, Netherlands7 Amsterdam University Medical Centres, Amsterdam, Netherlands8 Department of Internal Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Academisch Medisch Centrum, Amsterdam, Netherlands1 Department of Experimental Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Netherlands1 Department of Experimental Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Netherlands2 University of Amsterdam, Amsterdam, Netherlands1 Department of Experimental Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Netherlands3 Caelus Health, Heiloo, Netherlands3 Caelus Health, Heiloo, Netherlands4 Akkermansia Company, Mont-Saint-Guibert, Belgium6 Wageningen University, Wageningen, Netherlands9 Amsterdam UMC Locatie AMC, Amsterdam, NetherlandsBackground The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world’s population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles, and several microbial components have been implicated in MASLD pathophysiology. Indeed, earlier studies demonstrated that hepatic necroinflammation was reduced in individuals with MASLD after allogenic faecal microbiota transplantation (FMT) from healthy donors on a vegan diet. Here, we further investigate the therapeutic potential of gut microbiome modulation using a syntrophic combination of next-generation beneficial bacteria with FMT in individuals with advanced MASLD.Methods and analysis This trial is a randomised, double-blind, placebo-controlled study investigating the therapeutic potential of lyophilised faecal microbiota capsules (LFMCs) in individuals with metabolic dysfunction-associated steatohepatitis. In this study, 48 participants will be randomised 1:1 to receive either healthy vegan donor LFMCs or placebo for 24 weeks. In addition, all participants will be supplemented with a set of next-generation beneficial bacteria, including Anaerobutyricum soehngenii, pasteurised Akkermansia muciniphila and Bifidobacterium animalis subsp. lactis, as well as fructo-oligosaccharides. A liver biopsy will be performed at baseline and at the end of the trial. In addition, participants will be assessed through MRI, FibroScan, blood tests, faecal samples and continuous glucose monitoring. The first participant was enrolled on 25 April 2023.Ethics and dissemination Ethical approval was obtained from the Medical Ethics Committee of the University Medical Centre of Amsterdam. The results of this study will be disseminated through peer-reviewed journals.Trial Registration number The trial is registered on clinicaltrials.gov (NCT05821010).https://bmjopen.bmj.com/content/15/1/e088290.full |
| spellingShingle | Joanne Verheij Hilde Herrema Max Nieuwdorp Koen Wortelboer Aldo Grefhorst Quinten J. J. Augustijn Pleun de Groen Jos F ML Seegers Ismail Sahin Gül Peter Suenaert Willem M. de Vos Adriaan G. Holleboom Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis BMJ Open |
| title | Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis |
| title_full | Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis |
| title_fullStr | Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis |
| title_full_unstemmed | Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis |
| title_short | Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis |
| title_sort | randomised double blind placebo controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next generation beneficial bacteria in individuals with metabolic dysfunction associated steatohepatitis |
| url | https://bmjopen.bmj.com/content/15/1/e088290.full |
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