PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: NCT04006873 (02/07/2019).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: NCT04006873 (02/07/2019).
摘要：
■囊性纤维化（CF）患者可能会反复出现胸部感染，胰腺外分泌功能不全和胃肠道症状。新的囊性纤维化跨膜传导调节因子（CFTR）调节药物可改善肺功能，但胃肠道作用尚不清楚。我们的目的是看看CFTR调制器(tezacaftor-ivacaftor，TEZ/IVA）改善CF的胃肠道结局。
■我们进行了随机，双盲,安慰剂对照,诺丁汉大学医院两期交叉试验（2019-2020年）。使用MRI测量TEZ/IVA对肠道生理的影响。参与者被随机分配到治疗序列AB或BA(A：TEZ/IVA，B：安慰剂，每28天)，有28天的冲洗期。参与者在基线和每次治疗19-23天后进行了系列MRI扫描。由于COVID-19大流行，一项方案修订允许在TEZ/IVA之前和期间进行观察者-盲比较.在这种情况下,参与者并非对治疗视而不见,但研究人员仍然视而不见.主要结果是口盲肠转运时间（OCTT）。次要结果包括MRI指标，症状和粪便生物标志物。
■我们随机分配了13名参与者。在COVID-19大流行之前，有8名参与者完成了完整的方案，其中1名退出。其余4名参与者遵循修订后的协议。对于OCTT，安慰剂和TEZ/IVA之间没有显着差异（TEZ/IVA>360分钟[225，>360]与安慰剂330分钟[285，>360]，p=0.8）或次要结果。无不良事件发生。
■我们的数据有助于CFTR调节剂肺外效应的研究空白。我们发现TEZ/IVA后对肠道功能的MRI指标没有影响，胃肠道症状或大便钙卫蛋白。通过更大的研究可能可以检测到影响，更长的治疗或更有效的CFTR调节剂。
■NCT04006873（02/07/2019）。
■我们进行了随机，双盲,安慰剂对照,诺丁汉大学医院两期交叉试验（2019-2020年）。使用MRI测量TEZ/IVA对肠道生理的影响。参与者被随机分配到治疗序列AB或BA(A：TEZ/IVA，B：安慰剂，每28天)，有28天的冲洗期。参与者在基线和每次治疗19-23天后进行了系列MRI扫描。由于COVID-19大流行，一项方案修订允许在TEZ/IVA之前和期间进行观察者-盲比较.在这种情况下,参与者并非对治疗视而不见,但研究人员仍然视而不见.主要结果是口盲肠转运时间（OCTT）。次要结果包括MRI指标，症状和粪便生物标志物。
■我们随机分配了13名参与者。在COVID-19大流行之前，有8名参与者完成了完整的方案，其中1名退出。其余4名参与者遵循修订后的协议。对于OCTT，安慰剂和TEZ/IVA之间没有显着差异（TEZ/IVA>360分钟[225，>360]与安慰剂330分钟[285，>360]，p=0.8）或次要结果。无不良事件发生。
■我们的数据有助于CFTR调节剂肺外效应的研究空白。我们发现TEZ/IVA后对肠道功能的MRI指标没有影响，胃肠道症状或大便钙卫蛋白。通过更大的研究可能可以检测到影响，更长的治疗或更有效的CFTR调节剂。
■NCT04006873（02/07/2019）。
