Cystic FibrosisGIFT-CF3NCT04618185
Gut Imaging for Function & Transit in CF - GIFT-CF 3
An observational study of Cystic Fibrosis, run by Nottingham University Hospitals NHS Trust at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 to 60 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Magnetic Resonance Imaging (MRI)
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Oct 2020to 28 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 60 years
- All sexes
- Child, Adult
Study population: 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.
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire, NG7 2UH
About this study
Official title: Gut Imaging for Function & Transit in CF - GIFT-CF 3: Evaluation of Triple Combination Therapy.
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.
Read more
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
Read the 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.*
- Conditions
- Cystic Fibrosis
- Being tested
- Magnetic Resonance Imaging (MRI)
- Keywords
- Magnetic Resonance Imaging, Oro-caecal transit time, Small bowel water, Colonic volume, Gastrointestinal symptoms, Stool and sputum microbiome, CFTR modulator
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance Imaging (MRI)Diagnostic test
MRI to study gut function and transit without the risk of exposure to ionising radiation.
| Study group | Role | What they receive |
|---|---|---|
| p.Phe508del homozygous genotype | People with CF with 2 copies of p.Phe508del and previously eligible for Symkevi (Tezacaftor/Ivacaftor) Receives: Diagnostic Test: Magnetic Resonance Imaging (MRI) | |
| p.Phe508del heterozygous genotype | People with CF with 1 copy of p.Phe508del and not previously eligible for any CFTR modulator Receives: Diagnostic Test: Magnetic Resonance Imaging (MRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 days of scanning
Secondary outcomes (13)
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
Measured: 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
Measured: 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
Measured: 4 days of scanning
Stool calprotectin at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of gut inflammation
Measured: 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
Measured: 4 days of scanning
Stool elastase at baseline, 12 weeks, 24 weeks and 76 weeks
A marker of pancreatic exocrine function
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 4 days of scanning
Spirometry (FEV1) at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of lung function
Measured: 4 days of scanning
Weight (kg) at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of body mass
Measured: 4 days of scanning
Height (m) at baseline, 12 weeks, 24 weeks and 76 weeks
A measure of growth
Measured: 4 days of scanning
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2020
- Study start21 Oct 2020
- Primary completion28 Jun 2023
- Study completion28 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nottingham University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Manchester Metropolitan University, Vertex Pharmaceuticals Incorporated
- Responsible party
- Sponsor
- Investigators
- Alan Smyth, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04618185
- Sponsor's protocol ID
- 20CS036
- Acronym
- GIFT-CF3
- Status last verified
- May 2024
- First submitted
- 23 Oct 2020
- Last updated
- 23 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Imaging for Function & Transit in CF - GIFT-CF 3: Evaluation of Triple Combination Therapy.
- ClinicalTrials.gov ID
- NCT04618185
- Acronym / sponsor ID
- GIFT-CF3 / 20CS036
- Conditions
- Cystic Fibrosis
- Keywords
- Magnetic Resonance Imaging, Oro-caecal transit time, Small bowel water, Colonic volume, Gastrointestinal symptoms, Stool and sputum microbiome, CFTR modulator
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Nottingham University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- Manchester Metropolitan University, Vertex Pharmaceuticals Incorporated
- Study start
- 21 Oct 2020 (actual)
- Primary completion
- 28 Jun 2023 (actual)
- Study completion
- 28 Jun 2023 (actual)
- First posted
- 5 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
*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.*
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| p.Phe508del homozygous genotype | – | Diagnostic Test: Magnetic Resonance Imaging (MRI)People with CF with 2 copies of p.Phe508del and previously eligible for Symkevi (Tezacaftor/Ivacaftor) |
| p.Phe508del heterozygous genotype | – | Diagnostic Test: Magnetic Resonance Imaging (MRI)People with CF with 1 copy of p.Phe508del and not previously eligible for any CFTR modulator |
Who may qualify
- Ages
- 12 to 60 years
- Sex
- All
- Age groups
- Child, Adult
- Study population
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnetic Resonance Imaging (MRI)MRI to study gut function and transit without the risk of exposure to ionising radiation. | Diagnostic test | p.Phe508del heterozygous genotype, p.Phe508del homozygous genotype |
Primary outcome
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
13 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
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
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
Time frame: 4 days of scanning
Stool calprotectin at baseline, 12 weeks, 24 weeks and 76 weeks
Time frame: 4 days of scanning
Stool and sputum microbiome at baseline, 12 weeks, 24 weeks and 76 weeks
Time frame: 4 days of scanning
Stool elastase at baseline, 12 weeks, 24 weeks and 76 weeks
Time frame: 4 days of scanning
Terminal ileum motility at baseline, 12 weeks, 24 weeks and 76 weeks
Time frame: 4 days of scanning
Abdominal symptoms as measured by the CFAbd-Score
Time frame: 4 days of scanning
Abdominal symptoms as measured by the PAC-SYM score
Time frame: 4 days of scanning
Abdominal symptoms as measured by 3 domains from the Gastrointestinal Symptoms Rating Scale (GSRS)
Time frame: 4 days of scanning
Spirometry (FEV1) at baseline, 12 weeks, 24 weeks and 76 weeks
Time frame: 4 days of scanning
Weight (kg) at baseline, 12 weeks, 24 weeks and 76 weeks
Time frame: 4 days of scanning
Height (m) at baseline, 12 weeks, 24 weeks and 76 weeks
Time frame: 4 days of scanning
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan Smyth principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis, run by Nottingham University Hospitals NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2024.