ENHANCE- Establishing Natural History in an Advanced New CF Care Era

Establishing Natural History in an Advanced New CF Care Era

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Quality of Life

• Study Type: Observational
• Enrollment (Estimated): 550

Contacts and Locations

• Study Contact: Name: Karen Lester, PhD; Phone Number: (01) 4096500; Email: karenlester@rcsi.com
• Study Contact Backup: Name: Rachel Cregan, MSc; Phone Number: (01) 4096500; Email: rachelcregan@rcsi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• 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).

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; Newborn infants diagnosed with Cystic Fibrosis at newborn screening	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; Children with previous diagnosis of Cystic Fibrosis up to 5 years of age	Other: Quality of Life; ENHANCE will collect natural history on all children with cystic fibrosis who are enrolled over a 5 year period
Control; Newborn infants without cystic fibrosis	Other: Quality of Life; ENHANCE will collect natural history on all children with cystic fibrosis who are enrolled over a 5 year period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
4. The prevalence, natural history and progression of exocrine pancreatic dysfunction	Faecal Elastase Analysis	60 Months
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	Sweat chloride	60 Months
1. The incidence, prevalence and progression of structural lung disease	Spirometry-controlled Computed Tomography	60 Months
2. The long-term natural history of pulmonary function and ventilation homogeneity.	Spirometry, Multiple Breath Washout	60 Months
3. The incidence, prevalence and longitudinal progression of CF liver disease.	Liver Ultrasound, Liver Function Tests	60 Months
5. The longitudinal natural history of gastrointestinal symptoms, inflammation and the gut microbiome compared to a healthy control population	Microbiome Analysis, Identification of inflammatory markers, Abdominal Symptom Scores	60 Months
7. The longitudinal natural history of mental health outcomes in children with CF compared to controls.	Mental Health Quality Of Life Questionnaires	60 Months

Collaborators and Investigators

• Sponsor: Royal College of Surgeons, Ireland
• Collaborators: The Hospital for Sick Children; Massachusetts General Hospital; Belfast Health and Social Care Trust; NHS Lothian; Manchester University NHS Foundation Trust; Royal Brompton & Harefield NHS Foundation Trust; Cardiff and Vale University Health Board; Newcastle-upon-Tyne Hospitals NHS Trust; Alder Hey Children's NHS Foundation Trust; Erasmus University Rotterdam; Cork University Hospital; University Hospital of Limerick; Teagasc; University College Hospital Galway; Medizinische Hochschule Brandenburg Theodor Fontane
• Investigators: Principal Investigator: Paul McNally, RCSI

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: August 3, 2023
• First Submitted That Met QC Criteria: August 3, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis
• Other Study ID Numbers: ENHANCE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No