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

NCT05986045 | Not Yet Recruiting

• 1 other identifier: ENHANCE
• Study Type: observational
• Target: 550
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (7)

• 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

• 4. The prevalence, natural history and progression of exocrine pancreatic dysfunction

  Faecal Elastase Analysis

  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

• 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

• 7. The longitudinal natural history of mental health outcomes in children with CF compared to controls.

  Mental Health Quality Of Life Questionnaires

  60 Months

Study Arms (3)

Cohort 1

Newborn infants diagnosed with Cystic Fibrosis at newborn screening

Other: Quality of Life

Cohort 2

Children with previous diagnosis of Cystic Fibrosis up to 5 years of age

Other: Quality of Life

Control

Newborn infants without cystic fibrosis

Other: Quality of Life

Interventions

Quality of Life OTHER

ENHANCE will collect natural history on all children with cystic fibrosis who are enrolled over a 5 year period

Cohort 1; Cohort 2; Control

Eligibility Criteria

• Age: 1 Month - 5 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• 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).

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Quality of Life

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health

Study Officials

• Paul McNally

  RCSI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karen Lester, PhD

CONTACT

(01) 4096500; karenlester@rcsi.com

Rachel Cregan, MSc

CONTACT

(01) 4096500; rachelcregan@rcsi.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 14, 2023
• Study Start: October 1, 2023
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: August 31, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share