A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. [version 2; peer review: 2 approved]
Background People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We ai...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2024-03-01
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| Series: | NIHR Open Research |
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| Online Access: | https://openresearch.nihr.ac.uk/articles/3-65/v2 |
| _version_ | 1827301741895352320 |
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| author | Christabella Ng Helen Barr Caroline Hoad Neele S Dellschaft Robin Spiller Luca Marciani Alan R Smyth Trevor Hill Colin Crooks Jochen G Mainz Alex Menys Giles Major Penny A. Gowland |
| author_facet | Christabella Ng Helen Barr Caroline Hoad Neele S Dellschaft Robin Spiller Luca Marciani Alan R Smyth Trevor Hill Colin Crooks Jochen G Mainz Alex Menys Giles Major Penny A. Gowland |
| author_sort | Christabella Ng |
| collection | DOAJ |
| description | Background People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We aimed to see if a CFTR modulator (tezacaftor-ivacaftor,TEZ/IVA) improves gastrointestinal outcomes in CF. Methods We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers. Results We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA >360minutes [225,>360] vs. placebo 330minutes [285,>360], p=0.8) or secondary outcomes. There were no adverse events. Conclusions Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators. ClinicalTrials.gov registration NCT04006873 (02/07/2019) |
| first_indexed | 2024-04-24T16:31:31Z |
| format | Article |
| id | doaj.art-5c1c3656d9e84dffb5b38374c1d6241e |
| institution | Directory Open Access Journal |
| issn | 2633-4402 |
| language | English |
| last_indexed | 2024-04-24T16:31:31Z |
| publishDate | 2024-03-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | NIHR Open Research |
| spelling | doaj.art-5c1c3656d9e84dffb5b38374c1d6241e2024-03-30T01:00:00ZengF1000 Research LtdNIHR Open Research2633-44022024-03-01314726A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. [version 2; peer review: 2 approved]Christabella Ng0Helen Barr1https://orcid.org/0000-0002-4388-2563Caroline Hoad2Neele S Dellschaft3Robin Spiller4Luca Marciani5Alan R Smyth6https://orcid.org/0000-0001-5494-5438Trevor Hill7https://orcid.org/0000-0002-0277-4988Colin Crooks8Jochen G Mainz9Alex Menys10Giles Major11Penny A. Gowland12NIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKWolfson Adult Cystic Fibrosis Unit, Nottingham University Hospitals NHS Trust, Nottingham, UKNIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKNIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKNIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKNIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKNIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKNIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKNIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKCystic Fibrosis Centre, Brandenburg Medical School, Brandenburg an der Havel, GermanyCentre for Medical Imaging, Division of Medicine,, University College London, London, England, UKNottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, England, UKNIHR Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UKBackground People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We aimed to see if a CFTR modulator (tezacaftor-ivacaftor,TEZ/IVA) improves gastrointestinal outcomes in CF. Methods We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers. Results We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA >360minutes [225,>360] vs. placebo 330minutes [285,>360], p=0.8) or secondary outcomes. There were no adverse events. Conclusions Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators. ClinicalTrials.gov registration NCT04006873 (02/07/2019)https://openresearch.nihr.ac.uk/articles/3-65/v2cystic fibrosis gastrointestinal symptoms CFTR modulators magnetic resonance imaging.eng |
| spellingShingle | Christabella Ng Helen Barr Caroline Hoad Neele S Dellschaft Robin Spiller Luca Marciani Alan R Smyth Trevor Hill Colin Crooks Jochen G Mainz Alex Menys Giles Major Penny A. Gowland A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. [version 2; peer review: 2 approved] NIHR Open Research cystic fibrosis gastrointestinal symptoms CFTR modulators magnetic resonance imaging. eng |
| title | A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. [version 2; peer review: 2 approved] |
| title_full | A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. [version 2; peer review: 2 approved] |
| title_fullStr | A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. [version 2; peer review: 2 approved] |
| title_full_unstemmed | A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. [version 2; peer review: 2 approved] |
| title_short | A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. [version 2; peer review: 2 approved] |
| title_sort | randomised crossover trial of tezacaftor ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging mri outcomes a pilot study version 2 peer review 2 approved |
| topic | cystic fibrosis gastrointestinal symptoms CFTR modulators magnetic resonance imaging. eng |
| url | https://openresearch.nihr.ac.uk/articles/3-65/v2 |
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