Cystic FibrosisCFTR-MAGICNCT05253859
CFTR Modulators and Gastrointestinal Complications
An observational study of Cystic Fibrosis and Gastrointestinal System Disease, run by Nottingham University Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
To elucidate the similarities and distinctions in non-pulmonary manifestations of cystic fibrosis (CF) including distal intestinal obstruction syndrome (DIOS) incidence and pancreatic enzyme replacement therapy (PERT) use between US and UK CF populations in a parallel study using data from the UK and US CF registries. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cystic Fibrosis, Gastrointestinal System Disease, Distal Intestinal Obstruction Syndrome
- How many people
- 47,023 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2021to 10 Feb 2024
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Children, adolescents and adults with a diagnosis of cystic fibrosis whose data are registered on either the UK or US cystic fibrosis registries.
Who may be able to join
- All patients with CF of any genotype on the UK and US cystic fibrosis registries from the period 2007 - 2018.
Who cannot join
- Patients whose CFTR modulator status is unknown or only have one year of CFTR data recorded on the registry will be excluded from the analysis of the effects of CFTR modulators. This is to account for the fact that DIOS data is annualised on the registries, therefore there is no certainty at what time of year DIOS was diagnosed in relation to commencing CFTR modulator therapy.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Nottingham University Hospitals NHS Trust
Nottingham, NG7 2UH
About this study
To elucidate the similarities and distinctions in non-pulmonary manifestations of cystic fibrosis (CF) including distal intestinal obstruction syndrome (DIOS) incidence and pancreatic enzyme replacement therapy (PERT) use between US and UK CF populations in a parallel study using data from the UK and US CF registries. To assess how CFTR modulators impacted upon recorded PERT use and incidence of DIOS.
Read the detailed description
Cystic fibrosis (CF) is a autosomal recessive multi-system disorder caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As well as the documented respiratory complications of CF, gastrointestinal manifestations are of clinical importance. CFTR mutations in the gastrointestinal tract are responsible for pancreatic exocrine insufficiency in around 85% of people with CF (pwCF). In addition a severe gastrointestinal complication in CF is distal intestinal obstructive syndrome (DIOS), affecting 5.7% pwCF in the UK (2.5% in <16 years and 7.7% in adults) and 2.1% in the US (<18 years 1.7%, adult 2.4%) in 2019.
This is a parallel data registry study using data from the UK and US CF registries, with data provided for the time period 2007-2018. As such no individual participants will be recruited to the study. The CFTR modulators to be studies are Ivacaftor and lumacaftor/ivacaftor.
Study aims;
- Describe DIOS events and PERT usage in UK and US registries
- Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population time series
- Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series
The outcomes of the above aims will be used to generate hypotheses regarding the effect of the newer CFTR modulators such as Symdeko/Symkevi and Tricaftor/Kaftrio on PERT usage and DIOS incidence in CF registry data post 2018. This will form the basis of future studies.
- Conditions
- Cystic Fibrosis, Gastrointestinal System Disease, Distal Intestinal Obstruction Syndrome, Pancreatic Enzyme Abnormality, Pancreatic Disease, Lung Diseases
- Being tested
- No intervention
- Keywords
- Cystic fibrosis, Distal Intestinal Obstruction Syndrome, Pancreatic enzyme replacement therapy, Gastrointestinal symptoms, Gut symptoms
- Medical subject headings
- Cystic Fibrosis, Digestive System Diseases, Pancreatic Diseases, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
Registry study: No intervention
| Study group | Role | What they receive |
|---|---|---|
| Cystic fibrosis registry (UK) | People with cystic fibrosis registered in the UK CF registry Receives: Other: No intervention | |
| Cystic fibrosis registry (US) | People with cystic fibrosis registered in the US CF registry Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Describe DIOS events and PERT usage in UK and US registries 2007-2018
Descriptive analysis to include cumulative incidence of DIOS and prevalence of PERT usage in the UK and US. PERT use will be dichotomised (i.e use/no use), incidence of DIOS (event/no event), plotted by year, separated by registry. Trends will be described according to age range (<6, 6-11, 12+), sex, BMI, ethnicity, antibiotic use, gastrointestinal co-morbidities and FEV1 lung function.
These demographics will also be used for demographic propensity matching to define a control group of non-eligible non-users of CFTR modulators that are otherwise representative of the CFTR modulator user group the year that the CFTR modulator exposure was commenced.
Measured: 2 years
Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population level controlled interrupted time series (ITS)
This will investigate the effect of CFTR modulator intervention on the rate on PERT use and DIOS incidence.
ITS will explore proportion of DIOS events at population level in the CFTR modulator population and the propensity score defined comparator population. ITS will explore proportion of overall PERT usage (user/non user), and the proportion of individuals with a reduction in weight standardised PERT dose (decrease/no decrease).
Measured: 2 years
Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series
This will focus on patient level associations to complement the registry level findings. Associations in the incidence of PERT usage and DIOS events from 2012 in individuals taking CFTR modulators, compared to propensity matched controls will be explored.
DIOS events: Multilevel Poisson Regression model for count data by year, incidence rate ratio (frequency of DIOS events). Adjusted analysis for main covariates.
PERT use: Multilevel linear regression for continuous data, multilevel logistic regression for dichotomised data. Adjusted for main covariates.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2022
- Study start1 Oct 2021
- Primary completion10 Feb 2024
- Study completion10 Feb 2024
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
- Other
- Time perspective
- Retrospective
- Enrolment
- 47,023 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nottingham University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- The Leeds Teaching Hospitals NHS Trust, Royal Brompton & Harefield NHS Foundation Trust, University of Washington, Seattle Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Alan Smyth, Principal investigator, Nottingham University Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05253859
- Sponsor's protocol ID
- CFTR-MAGIC
- Acronym
- CFTR-MAGIC
- Status last verified
- Jul 2023
- First submitted
- 14 Feb 2022
- Last updated
- 3 Jul 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 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CFTR Modulators and Gastrointestinal Complications
- ClinicalTrials.gov ID
- NCT05253859
- Acronym / sponsor ID
- CFTR-MAGIC / CFTR-MAGIC
- Conditions
- Cystic Fibrosis, Gastrointestinal System Disease, Distal Intestinal Obstruction Syndrome, Pancreatic Enzyme Abnormality, Pancreatic Disease, Lung Diseases
- Keywords
- Cystic fibrosis, Distal Intestinal Obstruction Syndrome, Pancreatic enzyme replacement therapy, Gastrointestinal symptoms, Gut symptoms
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 47,023 participants (actual)
- Lead sponsor
- Nottingham University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- The Leeds Teaching Hospitals NHS Trust, Royal Brompton & Harefield NHS Foundation Trust, University of Washington, Seattle Children's Hospital
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 10 Feb 2024 (actual)
- Study completion
- 10 Feb 2024 (actual)
- First posted
- 24 Feb 2022 (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.
To elucidate the similarities and distinctions in non-pulmonary manifestations of cystic fibrosis (CF) including distal intestinal obstruction syndrome (DIOS) incidence and pancreatic enzyme replacement therapy (PERT) use between US and UK CF populations in a parallel study using data from the UK and US CF registries. To assess how CFTR modulators impacted upon recorded PERT use and incidence of DIOS.
Detailed description
Cystic fibrosis (CF) is a autosomal recessive multi-system disorder caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As well as the documented respiratory complications of CF, gastrointestinal manifestations are of clinical importance. CFTR mutations in the gastrointestinal tract are responsible for pancreatic exocrine insufficiency in around 85% of people with CF (pwCF). In addition a severe gastrointestinal complication in CF is distal intestinal obstructive syndrome (DIOS), affecting 5.7% pwCF in the UK (2.5% in <16 years and 7.7% in adults) and 2.1% in the US (<18 years 1.7%, adult 2.4%) in 2019.
This is a parallel data registry study using data from the UK and US CF registries, with data provided for the time period 2007-2018. As such no individual participants will be recruited to the study. The CFTR modulators to be studies are Ivacaftor and lumacaftor/ivacaftor.
Study aims;
- Describe DIOS events and PERT usage in UK and US registries
- Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population time series
- Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series
The outcomes of the above aims will be used to generate hypotheses regarding the effect of the newer CFTR modulators such as Symdeko/Symkevi and Tricaftor/Kaftrio on PERT usage and DIOS incidence in CF registry data post 2018. This will form the basis of future studies.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cystic fibrosis registry (UK) | – | Other: No interventionPeople with cystic fibrosis registered in the UK CF registry |
| Cystic fibrosis registry (US) | – | Other: No interventionPeople with cystic fibrosis registered in the US CF registry |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children, adolescents and adults with a diagnosis of cystic fibrosis whose data are registered on either the UK or US cystic fibrosis registries.
Key inclusion criteria (1 listed)
- All patients with CF of any genotype on the UK and US cystic fibrosis registries from the period 2007 - 2018.
Key exclusion criteria (1 listed)
- Patients whose CFTR modulator status is unknown or only have one year of CFTR data recorded on the registry will be excluded from the analysis of the effects of CFTR modulators. This is to account for the fact that DIOS data is annualised on the registries, therefore there is no certainty at what time of year DIOS was diagnosed in relation to commencing CFTR modulator therapy.
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 |
|---|---|---|
| No interventionRegistry study: No intervention | Other | Cystic fibrosis registry (UK), Cystic fibrosis registry (US) |
Primary outcome
Describe DIOS events and PERT usage in UK and US registries 2007-2018
Time frame: 2 years
Descriptive analysis to include cumulative incidence of DIOS and prevalence of PERT usage in the UK and US. PERT use will be dichotomised (i.e use/no use), incidence of DIOS (event/no event), plotted by year, separated by registry. Trends will be described according to age range (<6, 6-11, 12+), sex, BMI, ethnicity, antibiotic use, gastrointestinal co-morbidities and FEV1 lung function. These demographics will also be used for demographic propensity matching to define a control group of non-eligible non-users of CFTR modulators that are otherwise representative of the CFTR modulator user group the year that the CFTR modulator exposure was commenced.
Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population level controlled interrupted time series (ITS)
Time frame: 2 years
This will investigate the effect of CFTR modulator intervention on the rate on PERT use and DIOS incidence. ITS will explore proportion of DIOS events at population level in the CFTR modulator population and the propensity score defined comparator population. ITS will explore proportion of overall PERT usage (user/non user), and the proportion of individuals with a reduction in weight standardised PERT dose (decrease/no decrease).
Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series
Time frame: 2 years
This will focus on patient level associations to complement the registry level findings. Associations in the incidence of PERT usage and DIOS events from 2012 in individuals taking CFTR modulators, compared to propensity matched controls will be explored. DIOS events: Multilevel Poisson Regression model for count data by year, incidence rate ratio (frequency of DIOS events). Adjusted analysis for main covariates. PERT use: Multilevel linear regression for continuous data, multilevel logistic regression for dichotomised data. Adjusted for main covariates.
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 3 Jul 2024.
- Original article. "Pancreatic enzyme prescription following ivacaftor licensing: A retrospective analysis of the US and UK cystic fibrosis registries"Link provided by the sponsor.
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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
Nottingham University Hospitals NHS Trust
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 and Gastrointestinal System Disease, 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 1 inclusion and 1 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 3 Jul 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?
Describe DIOS events and PERT usage in UK and US registries 2007-2018 (time frame: 2 years). The study lists 3 primary outcomes in all. 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 3 Jul 2024; AzTrials last refreshed its copy on 30 Oct 2026.