Clinical trial NCT05986045: ENHANCE- Establishing Natural History in an Advanced New CF Care Era
Official title: Establishing Natural History in an Advanced New CF Care Era
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Cystic Fibrosis
Lead sponsor: Royal College of Surgeons, Ireland
Sponsor class: OTHER
Collaborators: name: University Hospital of Limerick
name: Cork University Hospital
name: University College Hospital Galway
name: Belfast Health and Social Care Trust
name: NHS Lothian
name: Alder Hey Children's NHS Foundation Trust
name: Manchester University NHS Foundation Trust
name: Newcastle-upon-Tyne Hospitals NHS Trust
name: Cardiff and Vale University Health Board
name: Royal Brompton & Harefield NHS Foundation Trust
name: Erasmus University Rotterdam
name: Medizinische Hochschule Brandenburg Theodor Fontane
name: Massachusetts General Hospital
name: The Hospital for Sick Children
name: Teagasc
First posted: 2023-08-14
Enrollment: 550
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All participants with CF will be invited to participate in ENHANCE. We will ensure a presentative mix of mutation groups, sex, ages, ethnicity and location in all cohorts. We will target recruitment to cohorts 1 and 2 based on the following split of mutations: 50% F508del homozygous(FF), 20%heterozygous for F508del and a minimum function mutation(FMF), 20% heterozygous for F508del and a residual function/gating mutation or gating/other mutation and 10% with no currently treatable mutation(NON).

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.


Eligibility criteria: Inclusion Criteria:

Children with CF attending one of the study centres and fulling one of the following:

* Newborn infant diagnoses with cystic fibrosis through newborn screening (excludes children with an uncertain diagnosis), or having 2 documented CF disease causing mutations.
* Children with CF (sweat chloride\>60mmol/L or 2 CF disease causing mutations) aged 0-6 at study initiation
* Healthy control infants without CF

Exclusion Criteria:

* Children or their parents not willing or able to complete with study procedures or assessments.
* 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.
* 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.
* 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

Primary outcomes:
measure: 1. The incidence, prevalence and progression of structural lung disease
timeFrame: 60 Months
measure: 2. The long-term natural history of pulmonary function and ventilation homogeneity.
timeFrame: 60 Months
measure: 3. The incidence, prevalence and longitudinal progression of CF liver disease.
timeFrame: 60 Months
measure: 4. The prevalence, natural history and progression of exocrine pancreatic dysfunction
timeFrame: 60 Months
measure: 5. The longitudinal natural history of gastrointestinal symptoms, inflammation and the gut microbiome compared to a healthy control population
timeFrame: 60 Months
measure: 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
timeFrame: 60 Months
measure: 7. The longitudinal natural history of mental health outcomes in children with CF compared to controls.
timeFrame: 60 Months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: RCSI
name: Paul McNally
role: PRINCIPAL_INVESTIGATOR
References: