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Completed

NCT Number: NCT04618185

Gut Imaging for Function & Transit in CF - GIFT-CF 3

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**

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

12 year–60 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

About this study

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.***

Who can participate

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Magnetic Resonance Imaging (MRI)

Diagnostic Test

MRI to study gut function and transit without the risk of exposure to ionising radiation.

Primary outcomes

  1. 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

  1. 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

    Time frame: 4 days of scanning

    A measure of small bowel water representing secretions

  2. Change in SBWC between 240 and 300 minutes (delta DTI) at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    These are small bowel water measurements before and after the second test meal

  3. Colonic volume area under the curve (AUC), corrected for body surface area at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    volume of colon representing ease of chyme passage through colon

  4. Stool calprotectin at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    A measure of gut inflammation

  5. Stool and sputum microbiome at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    A measure of types of microbiome present in the stool and sputum

  6. Stool elastase at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    A marker of pancreatic exocrine function

  7. Terminal ileum motility at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    A measure of motility at the terminal ileum using the GIQuant tool in arbitrary units

  8. Abdominal symptoms as measured by the CFAbd-Score

    Time frame: 4 days of scanning

    A measure of gut symptoms over the preceding 2 weeks and during the study day, where a high score indicates more severe abdominal symptoms

  9. Abdominal symptoms as measured by the PAC-SYM score

    Time frame: 4 days of scanning

    A measure of gut symptoms over the preceding 2 weeks and during the study day, where a high score indicates more severe abdominal symptoms

  10. Abdominal symptoms as measured by 3 domains from the Gastrointestinal Symptoms Rating Scale (GSRS)

    Time frame: 4 days of scanning

    A measure of gut symptoms over the preceding 2 weeks and during the study day,, where a high score indicates more severe abdominal symptoms

  11. Spirometry (FEV1) at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    A measure of lung function

  12. Weight (kg) at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    A measure of body mass

  13. Height (m) at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    A measure of growth

Other outcomes

  1. T1 relaxation of ascending colon chyme at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    An approximate measure of water content in chyme present in the ascending colon

  2. T2* of the terminal ileum

    Time frame: 4 days of scanning

    An approximate measure of gas bubbles in the terminal ileum

  3. Terminal ileum diameter at baseline, 12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    A measure of the diameter of the terminal ileum in millimeters

  4. Terminal ileum volume at baseline,12 weeks, 24 weeks and 76 weeks

    Time frame: 4 days of scanning

    Volume of the terminal ileum

  5. 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

    Time frame: 4 days of scanning

    Volume of the ascending colon, transverse colon, descending colon and rectosigmoid colon representing of chyme/faeces passage through individual segments of the colon

Sponsors and collaborators

Lead sponsor

Nottingham University Hospitals NHS Trust

Other

Collaborators

  • Manchester Metropolitan University
  • Vertex Pharmaceuticals Incorporated

Registry information

Official study title

Gut Imaging for Function & Transit in CF - GIFT-CF 3: Evaluation of Triple Combination Therapy.

Acronym: GIFT-CF3

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Nov 5, 2020
Registry last updated
May 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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