An observational study in Cystic Fibrosis, sponsored by Nottingham University Hospitals NHS Trust. Completed at 1 site in United Kingdom. Open to participants aged 12 Years to 60 Years. Per ClinicalTrials.gov, last updated 2024-05-23.
Sponsored by Nottingham University Hospitals NHS Trust · Observational
An observational study of patients with cystic fibrosis (CF) starting treatment with Kaftrio (Elexacaftor / Tezacaftor / Ivacaftor) as part of routine clinical care, following EMA licensing (approved end of Aug 2020).
Participants attend a study visit before Kaftrio treatment commences, followed by visits at 12 and 24 weeks after starting treatment. At each visit they will be scanned before and after standardised meals in the morning and mid-day (11 scans in total over 6 hours). No intravenous contrast or bowel preparation will be used. Participants will complete questionnaires on gastrointestinal symptoms as well as providing stool and sputum samples for assessment of microbiome and stool for inflammatory mediators and pancreatic function (elastase).
**Following an extension, participants had a further visit at 76 weeks post starting Kaftrio, updated in detailed description**
This is an observational study to observe the effects of Kaftrio (Elexacaftor / Tezacaftor / Ivacaftor) on the gut in people with CF.
Participants will attend 4 times, following an extension (pre-Kaftrio, at 12 weeks of Kaftrio at 24 weeks of Kaftrio and 76 weeks of Kaftrio) 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 and NCT04006873). 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.
They will also complete gut symptom questionnaires relating to the preceding 2 weeks and a 3 day food diary. They will also provide a sputum and stool sample.
Infection control requirements mean that only 1 participant will attend for MRI scanning per day. Extra COVID-19 precautions will also be taken throughout scan days.
***Please note, due to the timing of EMA approval for Kaftrio and ethics approval for the study granted on 21st Ocober 2020, the clinicaltrials.gov registration was created on 21st October 2020 and approved by the clinicaltrials.gov PRS team on 4th November 2020.***
1,581 studies on the registry are indexed under Cystic Fibrosis; 190 are open to participants now.
This study's enrollment of 24 is below the median of 85 across 482 observational studies indexed under Cystic Fibrosis.
Browse Cystic Fibrosis studies →Nottingham University Hospitals NHS Trust is the lead sponsor of 104 studies on the registry; 19 are open to participants now.
Counted across the registry records on this site, refreshed daily.
All CF patients who receive care by Nottingham University Hospitals NHS Trust and are eligible for the study will be approached by their usual care team.
Exclusion Criteria:
People with CF with 2 copies of p.Phe508del and previously eligible for Symkevi (Tezacaftor/Ivacaftor)
Diagnostic Test: Magnetic Resonance Imaging (MRI)
People with CF with 1 copy of p.Phe508del and not previously eligible for any CFTR modulator
Diagnostic Test: Magnetic Resonance Imaging (MRI)
MRI to study gut function and transit without the risk of exposure to ionising radiation.
Difference in oro-caecal transit time (OCTT) in minutes at baseline and 24 weeks and baseline and 76 weeks
the time when the test meal is first detectable in the caecum
Time frame: 4 days of scanning
Small bowel water content (SBWC) area under the curve (AUC), corrected for body surface area, measured in L.min/m^2 between 0 and 360 minutes at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of small bowel water representing secretions
Time frame: 4 days of scanning
Change in SBWC between 240 and 300 minutes (delta DTI) at baseline, 12 weeks, 24 weeks and 76 weeks
These are small bowel water measurements before and after the second test meal
Time frame: 4 days of scanning
Colonic volume area under the curve (AUC), corrected for body surface area at baseline, 12 weeks, 24 weeks and 76 weeks
volume of colon representing ease of chyme passage through colon
Time frame: 4 days of scanning
Stool calprotectin at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of gut inflammation
Time frame: 4 days of scanning
Stool and sputum microbiome at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of types of microbiome present in the stool and sputum
Time frame: 4 days of scanning
Stool elastase at baseline, 12 weeks, 24 weeks and 76 weeks
A marker of pancreatic exocrine function
Time frame: 4 days of scanning
Terminal ileum motility at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of motility at the terminal ileum using the GIQuant tool in arbitrary units
Time frame: 4 days of scanning
Abdominal symptoms as measured by the CFAbd-Score
A measure of gut symptoms over the preceding 2 weeks and during the study day, where a high score indicates more severe abdominal symptoms
Time frame: 4 days of scanning
Abdominal symptoms as measured by the PAC-SYM score
A measure of gut symptoms over the preceding 2 weeks and during the study day, where a high score indicates more severe abdominal symptoms
Time frame: 4 days of scanning
Abdominal symptoms as measured by 3 domains from the Gastrointestinal Symptoms Rating Scale (GSRS)
A measure of gut symptoms over the preceding 2 weeks and during the study day,, where a high score indicates more severe abdominal symptoms
Time frame: 4 days of scanning
Spirometry (FEV1) at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of lung function
Time frame: 4 days of scanning
Weight (kg) at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of body mass
Time frame: 4 days of scanning
Height (m) at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of growth
Time frame: 4 days of scanning
T1 relaxation of ascending colon chyme at baseline, 12 weeks, 24 weeks and 76 weeks
An approximate measure of water content in chyme present in the ascending colon
Time frame: 4 days of scanning
T2* of the terminal ileum
An approximate measure of gas bubbles in the terminal ileum
Time frame: 4 days of scanning
Terminal ileum diameter at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of the diameter of the terminal ileum in millimeters
Time frame: 4 days of scanning
Terminal ileum volume at baseline,12 weeks, 24 weeks and 76 weeks
Volume of the terminal ileum
Time frame: 4 days of scanning
Colonic volume area under the curve, corrected for body surface area, of individual segments of the colon i.e. ascending, transverse, descending and rectosigmoid colon at baseline, 12 weeks, 24 weeks and 76 weeks
Volume of the ascending colon, transverse colon, descending colon and rectosigmoid colon representing of chyme/faeces passage through individual segments of the colon
Time frame: 4 days of scanning
This study is completed, as verified in May 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Nottingham University Hospitals NHS Trust