Cystic FibrosisPhase 2GIFT-CF2NCT04006873
Gut Imaging for Function & Transit in Cystic Fibrosis Study 2
A Phase 2 study testing Tezacaftor/Ivacaftor + Ivacaftor in people with Cystic Fibrosis, run by Nottingham University Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 to 40 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Tezacaftor/Ivacaftor + Ivacaftor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Sep 2019to 29 Oct 2020
- Phase
- Phase 2
- 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 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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.
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: 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
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.
Read the detailed description
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.
Infection control requirements mean that only 1 participant will attend for MRI scanning per day.
*Amendment to study due to COVID-19* From mid-March 2020, all face to face clinical research in the UK has been suspended (apart from studies directly related to the COVID-19 pandemic). Patients in the GIFT-CF 2 trial who had not yet completed the full trial protocol were therefore unable to continue. Funding for SymkeviTM (tezacaftor/ivacaftor and ivacaftor) in the UK was announced at the end of 2019 and some of the trial participants, who have not completed GIFT-CF 2, may be prescribed SymkeviTM by their CF team. It will therefore not be possible for them to complete the placebo controlled cross-over trial, once COVID restrictions are eased. We plan to mitigate the effects of COVID-related disruption by ensuring all trial participants have had the full, protocol-defined, scan sequence both on and off SymkeviTM. When restrictions are eased, we will invite participants who have been prescribed SymkeviTM by their CF centre to attend for scanning, if they have not previously had an "on treatment" scan. We will follow the same scanning protocol. We will ensure that adherence to SymkeviTM is good and they have received at least 21 days of treatment (as specified in the trial protocol). Our primary analysis will be on the patients who completed the trial per protocol but we will present a secondary analysis on all 12 patients, comparing outcome measures on SymkeviTM with their outcome measures previously recorded at baseline (off treatment). The personnel interpreting the MRI scans will be blind to whether they were performed on or off SymkeviTM - reducing the probability of observer bias.
*Post hoc analysis* For participants who are invited for an open-label "on treatment" MRI scan day, the statistical analysis will involve a comparison between their pre-treatment MRI scans and the open-label scan. The researcher analysing the images will remain blinded. Statistical analysis for these participants will be a comparison between their pre-treatment scan and open-label on-treatment scan. Motility outcomes will not be analysed as the specific MR sequencing was adapted to focus on the terminal ileum in the cross-over trial, whilst in the pre-treatment scans, the motility was across the whole small bowel.
- Conditions
- Cystic Fibrosis
- Being tested
- Tezacaftor/Ivacaftor + Ivacaftor, Placebo oral tablet
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tezacaftor/Ivacaftor + IvacaftorDrug
Also called VX-661 100mg / VX-770 150mg active tablets, VX-770 150mg active tablets
As per description in arms.
Placebo oral tabletDrug
Also called Matching placebo tablets
As per description in arms
| Study group | Role | What they receive |
|---|---|---|
| Tezacaftor/Ivacaftor in combination with Ivacaftor | Active comparator | 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. Receives: Drug: Tezacaftor/Ivacaftor + Ivacaftor |
| Placebo | Placebo comparator | A visually matched placebo to the active drugs will be taken in the morning and in the evening for 28 days. Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oro-caecal Transit Time
Time taken after eating for ingested food to be identifiable at the caecum on MRI
Measured: 1 day of scanning
Secondary outcomes (4)
Gastric volume
Volume of stomach at each time point of digestion to measure gastric emptying time
Measured: 1 day of scanning
Small bowel water content (corrected for body surface area)
Volume of water content in small bowel representing secretions and post prandial change in small bowel water content at T240 and T300
Measured: 1 day of scanning
Colonic volume (corrected for body surface area)
Volume of colon representing ease of chyme passage through colon
Measured: 1 day of scanning
Gastrointestinal symptoms
Gastrointestinal symptoms measured by patient reported outcomes to monitor relationships with outcomes measure by MRI
Measured: 1 day 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 Jul 2019
- Study start3 Sep 2019
- Primary completion29 Oct 2020
- Study completion29 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nottingham University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Vertex Pharmaceuticals Incorporated, Cystic Fibrosis Foundation, Cystic Fibrosis Trust, University of Nottingham
- Responsible party
- Sponsor
- Investigators
- Alan Smyth, Prof, Principal investigator, University of NottinghamGiles Major, Dr, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04006873
- Sponsor's protocol ID
- 18RM039
- Acronym
- GIFT-CF2
- Status last verified
- May 2023
- First submitted
- 2 Jul 2019
- Last updated
- 24 May 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data can be obtained by reasonable request to the study Principal Investigator and corresponding author Professor Alan Smyth (alan.smyth@nottingham.ac.uk) This will be assessed on a case-by-case basis. Applications should state the research question being addressed and include a link to the researcher's published protocol. This will be reviewed by the research team and a final decision to share data the responsibility of the Principal Investigator.
Publications
Ng C, Dellschaft NS, Hoad C, Marciani L, Spiller R, Crooks C, Hill T, Menys A, Mainz JG, Barr H, Gowland PA, Major G, Smyth AR. A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. NIHR Open Res. 2024 Mar 19;3:65. doi: 10.3310/nihropenres.13510.2. eCollection 2023.
PubMed 39139270
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04006873
- Acronym / sponsor ID
- GIFT-CF2 / 18RM039
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Nottingham University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- Vertex Pharmaceuticals Incorporated, Cystic Fibrosis Foundation, Cystic Fibrosis Trust, University of Nottingham
- Study start
- 3 Sep 2019 (actual)
- Primary completion
- 29 Oct 2020 (actual)
- Study completion
- 29 Oct 2020 (actual)
- First posted
- 5 Jul 2019 (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.
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.
Detailed description
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.
Infection control requirements mean that only 1 participant will attend for MRI scanning per day.
*Amendment to study due to COVID-19* From mid-March 2020, all face to face clinical research in the UK has been suspended (apart from studies directly related to the COVID-19 pandemic). Patients in the GIFT-CF 2 trial who had not yet completed the full trial protocol were therefore unable to continue. Funding for SymkeviTM (tezacaftor/ivacaftor and ivacaftor) in the UK was announced at the end of 2019 and some of the trial participants, who have not completed GIFT-CF 2, may be prescribed SymkeviTM by their CF team. It will therefore not be possible for them to complete the placebo controlled cross-over trial, once COVID restrictions are eased. We plan to mitigate the effects of COVID-related disruption by ensuring all trial participants have had the full, protocol-defined, scan sequence both on and off SymkeviTM. When restrictions are eased, we will invite participants who have been prescribed SymkeviTM by their CF centre to attend for scanning, if they have not previously had an "on treatment" scan. We will follow the same scanning protocol. We will ensure that adherence to SymkeviTM is good and they have received at least 21 days of treatment (as specified in the trial protocol). Our primary analysis will be on the patients who completed the trial per protocol but we will present a secondary analysis on all 12 patients, comparing outcome measures on SymkeviTM with their outcome measures previously recorded at baseline (off treatment). The personnel interpreting the MRI scans will be blind to whether they were performed on or off SymkeviTM - reducing the probability of observer bias.
*Post hoc analysis* For participants who are invited for an open-label "on treatment" MRI scan day, the statistical analysis will involve a comparison between their pre-treatment MRI scans and the open-label scan. The researcher analysing the images will remain blinded. Statistical analysis for these participants will be a comparison between their pre-treatment scan and open-label on-treatment scan. Motility outcomes will not be analysed as the specific MR sequencing was adapted to focus on the terminal ileum in the cross-over trial, whilst in the pre-treatment scans, the motility was across the whole small bowel.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tezacaftor/Ivacaftor in combination with Ivacaftor | Active comparator | Drug: Tezacaftor/Ivacaftor + IvacaftorA 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. |
| Placebo | Placebo comparator | Drug: Placebo oral tabletA visually matched placebo to the active drugs will be taken in the morning and in the evening for 28 days. |
Who may qualify
- Ages
- 12 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| Tezacaftor/Ivacaftor + IvacaftorAlso: VX-661 100mg / VX-770 150mg active tablets, VX-770 150mg active tabletsAs per description in arms. | Drug | Tezacaftor/Ivacaftor in combination with Ivacaftor |
| Placebo oral tabletAlso: Matching placebo tabletsAs per description in arms | Drug | Placebo |
Primary outcome
Oro-caecal Transit Time
Time frame: 1 day of scanning
Time taken after eating for ingested food to be identifiable at the caecum on MRI
4 secondary outcomes
Gastric volume
Time frame: 1 day of scanning
Small bowel water content (corrected for body surface area)
Time frame: 1 day of scanning
Colonic volume (corrected for body surface area)
Time frame: 1 day of scanning
Gastrointestinal symptoms
Time frame: 1 day 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 24 May 2023.
- Derived from this study: PubMed 39139270Ng C, Dellschaft NS, Hoad C, Marciani L, Spiller R, Crooks C, Hill T, Menys A, Mainz JG, Barr H, Gowland PA, Major G, Smyth AR. A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. NIHR Open Res. 2024 Mar 19;3:65. doi: 10.3310/nihropenres.13510.2. eCollection 2023.
- Individual participant dataSharing planned: Yes. The data can be obtained by reasonable request to the study Principal Investigator and corresponding author Professor Alan Smyth (alan.smyth@nottingham.ac.uk) This will be assessed on a case-by-case basis. Applications should state the research question being addressed and include a link to the researcher's published protocol. This will be reviewed by the research team and a final decision to share data the responsibility of the Principal Investigator.
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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, Prof principal investigator
University of Nottingham
Giles Major, Dr 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?
A Phase 2 study testing Tezacaftor/Ivacaftor + Ivacaftor in people with 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 2 inclusion and 11 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 24 May 2023. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Oro-caecal Transit Time (time frame: 1 day of scanning). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04006873, which also lists 1 linked publication.
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 24 May 2023.