Gut Imaging for Function and Transit in Cystic Fibrosis 3 Junior

NCT05699148 | Unknown

• 1 other identifier: 20CS036 sub-study
• Study Type: observational
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Recently trial data has shown that the medicine KaftrioTM (Elexacaftor/ Tezacaftor/ Ivacaftor) improves lung function in children aged 6 to 11 years who have cystic fibrosis (CF). This has led to it being licensed for use in the UK in 2022 and is now being prescribed in this age group. There is little information in trials however that shows the effect KaftrioTM (ETI) has on the gut or liver in this age group. Previous studies in the GIFT-CF series (NCT 03566550, NCT04006873 and NCT04618185) has found differences in the functioning of the gut between adults with CF and healthy controls but it is not known whether these differences are present in those aged 6 to 11 years. This study is a significant amendment of the GIFT-CF3 protocol (NCT04618185) that aims to measure gut function using magnetic resonance imaging (MRI) in children with CF before and after starting ETI. This study also aims to opportunistically measure lung function and structure using MRI and explore how the liver can be measured using MRI in this age group. The study is split into 2 stages. The first is a pilot stage using the modified GIFT-CF protocol recruiting 3 children with CF before starting ETI and 3 healthy volunteers. This is to determine we are able to successfully perform these scans in these age groups. If successful, the second stage will recruit a further 12 children with CF before they start ETI. This will take our cohort up to 15 children with CF. This cohort will then be rescanned 6 months after starting ETI using the same scan protocol.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; CFTR modulators; Gastrointestinal; Lung; Liver; Magnetic resonance imaging; Elexacaftor/ tezacaftor/ ivacaftor

Outcome Measures

Primary Outcomes (1)

• Delta Small Bowel Water (DeltaSBW)

  This measurement relates to the postprandial fall in small bowel water content post second study meal. This will be adjusted to body surface area (mL/m2)

  This a measure of the change in small bowel water between study time points 240 minutes and 300 minutes post first study meal.

Secondary Outcomes (4)

• Small bowel water content

  Will be measured at study timepoints: baseline, 240 minutes and 300 minutes and then area under the curve calculated using the three timepoints (L.min/m2)

• Liver volume

  Measured during fasted, baseline MRI scan

• Liver elastography

  Measured during fasted, baseline MRI scan

• Lung ventilation

  Measured at 240 minute time point

Study Arms (2)

Children with cystic fibrosis aged 6 to 11 years

Group of children who have at least one copy of Phe508del gene mutation and are eligible for starting on the modulator elexacaftor/ tezacaftor/ ivacaftor (ETI). This group will have baseline MRI scans before starting ETI and aiming to have subsequent scans post starting ETI (6 months to 1 year post starting ETI)

Drug: Elexacaftor / Ivacaftor / Tezacaftor

Control Group

Age and gender matched controls with no history of cystic fibrosis or gastrointestinal disease. This group will undergo one set of scans only.

Interventions

Elexacaftor / Ivacaftor / Tezacaftor DRUG

Triple combination therapy is licensed in the UK for prescription to paediatric patients aged 6 to 11 years. ETI will be started as part of routine clinical care.

Also known as: Kaftrio, Trikafta

Children with cystic fibrosis aged 6 to 11 years

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children with CF aged 6 to 11 years. Must have at least one copy of the Phe508del mutation. These children would be planned to start receiving ETI as part of their routine clinical care.

You may qualify if:

• Children with CF aged 6 to 11 years. Must have at least one copy of the Phe508del mutation.
• Healthy volunteers must have no previous history of gastrointestinal disease.

You may not qualify if:

• Healthy volunteers with a history of gastrointestinal disease.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead

Study Sites (1)

Queen's Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

elexacaftor, ivacaftor, tezacaftor drug combination

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

Study Officials

• Andrew Prayle

  Associate Professor

  PRINCIPAL INVESTIGATOR

• Alan Smyth

  Professor of Child Health

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 10, 2023
• First Posted: January 26, 2023
• Study Start: April 1, 2022
• Primary Completion: August 1, 2022
• Study Completion: April 1, 2023
• Last Updated: January 26, 2023

Record last verified: 2023-01

Locations

GB (1)