Gut Imaging for Function & Transit in CF - GIFT-CF 3: Evaluation of Triple Combination Therapy.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Difference in oro-caecal transit time (OCTT) in minutes at baseline and 24 weeks and baseline and 76 weeks
Study Overview
Brief Summary
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).
- Patients with CF who are p.Phe508del homozygotes will already be receiving the less effective CFTR modulator drug Symkevi (Tezacaftor / Ivacaftor) and will switch to KaftrioTM.
- Patients who are who are compound heterozygotes with at least 1 copy of p.Phe508del currently have access to no effective CFTR modulator and will be starting a CFTR modulator (Kaftrio) for the first time.
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**
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 12 Years to 60 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 12 - 60 years
- •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.
- •Genotype homozygous p.Phe508del or compound heterozygous with at least 1 copy of p.Phe508del.
- •Eligible for KaftrioTM (Elexacaftor / Tezacaftor / Ivacaftor) treatment but not yet commenced Kaftrio treatment as part of routine care.
Exclusion Criteria
- •Contra-indication to MRI scanning, such as embedded metal, pacemaker.
- •FEV1 < 40% (% predicted using Global Lung Initiative values)
- •Unable to stop medications directly prescribed to alter bowel habit, such as laxatives of anti-diarrhoeals, on the study day
- •Previous resection of small bowel >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
- •Pregnancy - tests are available at the SPMIC if participants are unsure
- •Unable to speak or understand English
Outcomes
Primary Outcomes
Difference in oro-caecal transit time (OCTT) in minutes at baseline and 24 weeks and baseline and 76 weeks
Time Frame: 4 days of scanning
the time when the test meal is first detectable in the caecum
Secondary Outcomes
- 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(4 days of scanning)
- Change in SBWC between 240 and 300 minutes (delta DTI) at baseline, 12 weeks, 24 weeks and 76 weeks(4 days of scanning)
- Abdominal symptoms as measured by the PAC-SYM score(4 days of scanning)
- Spirometry (FEV1) at baseline, 12 weeks, 24 weeks and 76 weeks(4 days of scanning)
- Weight (kg) at baseline, 12 weeks, 24 weeks and 76 weeks(4 days of scanning)
- Height (m) at baseline, 12 weeks, 24 weeks and 76 weeks(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(4 days of scanning)
- Stool and sputum microbiome at baseline, 12 weeks, 24 weeks and 76 weeks(4 days of scanning)
- Terminal ileum motility at baseline, 12 weeks, 24 weeks and 76 weeks(4 days of scanning)
- Stool calprotectin at baseline, 12 weeks, 24 weeks and 76 weeks(4 days of scanning)
- Stool elastase at baseline, 12 weeks, 24 weeks and 76 weeks(4 days of scanning)
- Abdominal symptoms as measured by the CFAbd-Score(4 days of scanning)
- Abdominal symptoms as measured by 3 domains from the Gastrointestinal Symptoms Rating Scale (GSRS)(4 days of scanning)