A Randomised Crossover Pilot Study of the Effects of Tezacaftor/Ivacaftor and Ivacaftor on Gastrointestinal Function Using Magnetic Resonance Imaging Parameters in People With Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Oro-caecal Transit Time
研究概览
简要总结
People with Cystic Fibrosis (CF) have problems digesting their food properly. More than 8 in 10 people with CF must take medication to assist their digestion. In spite of this, complications such as bowel blockage occur.
Finding out how already licenced drugs for CF work in the gut is the first step in repurposing medications. Tezacaftor/Ivacaftor with Ivacaftor is a drug combination which corrects the basic defect in CF an has shown improvements on lung function.
The purpose of this study is to evaluate, using Magnetic Resonance Imaging (MRI) and patient-reported outcomes, whether Tezacaftor/Ivacaftor with Ivacaftor has an effect on improving gastrointestinal problems in CF.
详细描述
This is a small pilot study to compare the effects of active drug (Tezacaftor/Ivacaftor with Ivacaftor) on the gut in people with CF.
Participants will be randomised to take active drug or matched placebo for 28 days then switch to the alternate drug after a 28 day washout period. Before participants commence treatment, they will have blood pressure and baseline blood tests.
Participants will attend once per treatment period for MRI scanning at the Sir Peter Mansfield Imaging Centre, after an overnight fast. On this day, participants will be asked to withhold any medicines directly altering bowel habit such as laxatives. They will continue to take pancreatic enzyme replacement therapy and other medications for CF.
The Investigators will use the same MRI protocol as described in GIFT-CF (NCT03566550). Participants will have their first MRI scan fasted. After the first scan, they will eat a first standardised meal . They will then have 7 MRI scans at half hourly intervals and 3 MRI scans at hourly intervals. Participants will be given a second standardised meal after their ninth MRI scan. Each MRI scan will last approximately 15 minutes. After each MRI scan, participants will complete a validated gastrointestinal symptom questionnaire (Gastrointestinal Symptom Rating Scale). In between scans, participants will have access to an adjacent room with Wifi and television access.
During the day, participants will have their lung function, blood pressure and blood tests taken. They will also provide a sputum and stool sample.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •capacity to consent, or to understand the requirements of the study where parental consent is needed
- •confirmed diagnosis of CF, either by sweat test or genetic testing. Tezacaftor/Ivacaftor is indicated only for patients homozygous for the commonest CF mutation - p.Phe508del and so we will enrol only CF patients with this genotype
排除标准
- •currently taking CFTR modulator drug
- •Contra-indication to use of Tezacaftor/Ivacaftor
- •Measurement of FEV1 <40% predicted using Global Lung Initiative criteria, according to clinical records, as participants will be required to perform a series of 10 second breathholds throughout MRI scanning
- •Contra-indication to MRI scanning, such as embedded metal, pacemaker.
- •Pregnancy
- •Unable to stop medications directly prescribed to alter bowel habit, such as laxatives or anti-diarrhoeals, on the study day
- •Previous resection of any part of the gastrointestinal tract apart from appendicectomy or cholecystectomy. Surgical relief of meconium ileus or DIOS will be permitted unless clinical records show excision of intestine >20cm in length.
- •Intestinal stoma
- •Diagnosis of inflammatory bowel disease or coeliac disease confirmed by biopsy
- •Gastrointestinal malignancy
- •Unable to comply with dietary restrictions required for the study.
研究组 & 干预措施
Tezacaftor/Ivacaftor in combination with Ivacaftor
A film-coated tablet containing 100mg tezacaftor and 150mg ivacaftor will be taken in the morning.
A film-coated tablet containing 150mg ivacaftor will be taken in the evening.
Participants will take these tablets for 28 days.
All tablets are licensed for use in the EU.
干预措施: Tezacaftor/Ivacaftor + Ivacaftor (Drug)
Placebo
A visually matched placebo to the active drugs will be taken in the morning and in the evening for 28 days.
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Oro-caecal Transit Time
时间窗: 1 day of scanning
Time taken after eating for ingested food to be identifiable at the caecum on MRI
次要结局
- Gastric volume(1 day of scanning)
- Small bowel water content (corrected for body surface area)(1 day of scanning)
- Colonic volume (corrected for body surface area)(1 day of scanning)
- Gastrointestinal symptoms(1 day of scanning)