ENHANCE- Establishing Natural History in an Advanced New CF Care Era
Study Details
Study Description
Brief Summary
Measured outcomes for people with CF have improved dramatically over the last 20 years, even prior to the widespread introduction of cystic fibrosis transmembrane conductance regulator (CTFR) modulator treatments. The outlook for children with CF has improved significantly, with longer predicted survival and a lower likelihood of morbidity. This has accelerated recently. These changes have occurred within a short period of time, and there is much that we now do not understand about disease progression in children with CF and how this differs from children without CF. CF is an area which is fortunate to have well-developed and successful disease registries. CF registries have provided significant amounts of very useful data to guide improvement in treatment and outcomes over many decades. The power of registries comes from the collection of a well-defined set of important outcome measures in very large numbers of people over many years.
The outcome measures collected routinely in clinical care, which form part of the registries, are helpful in monitoring moderate-advances and symptomatic disease in people with CF. CF registries however do not tend to collect tomography(CT) scores, lung clearance index(LCI) or indeed repeated collection of biomarkers of disease activity such as sweat chloride which are increasingly relevant in an era of modulator therapies and reducing burden of symptomatic disease. We perceive an urgent need to complement registry data, cataloguing the changing natural history if early childhood CF by proactively collecting and curating sensitive, meaningful outcome data in a large cohort of children during this new era in Ireland and the UK.
The prevalence, presentation and natural history of disease manifestation of CF in young children will change significantly in the next decade with advances in the understanding and treatment of CF, including the use of therapies aimed at CFTR function. ENHANCE provides an opportunity to study these changes in real-time and in ways that are relevant to the CF community.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Cohort 1 Neonatal people with cystic fibrosis up to the age of 2 years |
Other: Quality of Life
ENHANCE will collect natural history on all children with cystic fibrosis who are enrolled over a 5 year period
|
| Cohort 2 People with cystic fibrosis aged between 2-5 years of ages |
Other: Quality of Life
ENHANCE will collect natural history on all children with cystic fibrosis who are enrolled over a 5 year period
|
| Control People without cystic fibrosis and non-carriers of CF-related genes aged 0-6years |
Other: Quality of Life
ENHANCE will collect natural history on all children with cystic fibrosis who are enrolled over a 5 year period
|
Outcome Measures
Primary Outcome Measures
- 1. The incidence, prevalence and progression of structural lung disease [60 Months]
Spirometry, MBW
- 2. The long-term natural history of pulmonary function and ventilation homogeneity. [60 Months]
Spirometry-controlled CT
- 3. The incidence, prevalence and longitudinal progression of CF liver disease. [60 Months]
Liver Ultrasound, LFTs
- 4. The prevalence, natural history and progression of exocrine pancreatic dysfunction [60 Months]
Faecal Elastase Analysis
- 5. The longitudinal natural history of gastrointestinal symptoms, inflammation and the gut microbiome compared to a healthy control population [60 Months]
Microbiome Analysis, Identification of inflammatory markers
- 6. The longitudinal natural history of annual sweat chloride levels in infants and children of different ages, the influence of different treatments on this and its association with other outcomes [60 Months]
Sweat chloride
- 7. The longitudinal natural history of mental health outcomes in children with CF compared to controls. [60 Months]
Mental Health QOL Questionnaires
Eligibility Criteria
Criteria
Inclusion Criteria:
Children with CF attending one of the study centres and fulling one of the following:
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Newborn infant diagnoses with cystic fibrosis through newborn screening (excludes children with an uncertain diagnosis), or having 2 documented CF disease causing mutations.
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Children with CF (sweat chloride>60mmol/L or 2 CF disease causing mutations) aged 0-6 at study initiation
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Healthy control infants without CF
Exclusion Criteria:
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Children or their parents not willing or able to complete with study procedures or assessments.
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Co-morbidities in groups 1 and 2, unrelated to CF, that in the opinion of the investigator would substantially impact on study measurements and unduly affect the veracity of the outcome data, for example a diagnosis of inflammatory bowel disease or extreme prematurity.
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Children in the control group who are carriers of CFTR mutations or have chronic medical or GI/Liver conditions that in the opinion of the investigator would unduly affect the veracity of the outcome data.
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We will not exclude someone who subsequently joins a CF Investigational drug trial if they are happy to continue, but if possible, will time their annual ENHANCE data collection to fall outside the time period of any experimental study drug administration
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Royal College of Surgeons, Ireland
- University Hospital of Limerick
- Cork University Hospital
- University College Hospital Galway
- Belfast Health and Social Care Trust
- NHS Lothian
- Alder Hey Children's NHS Foundation Trust
- Manchester University NHS Foundation Trust
- Newcastle-upon-Tyne Hospitals NHS Trust
- Cardiff and Vale University Health Board
- Royal Brompton & Harefield NHS Foundation Trust
- Erasmus University Rotterdam
- Medizinische Hochschule Brandenburg Theodor Fontane
- Massachusetts General Hospital
- The Hospital for Sick Children
- Teagasc
Investigators
- Principal Investigator: Paul McNally, RCSI
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ENHANCE