CFTR Modulator Drugs and Inflammation in children with CF

  • Research type

    Research Study

  • Full title

    Identifying the effects of CFTR Modulators on the biochemical signalling pathways involved in inflammation in children with cystic fibrosis

  • IRAS ID

    304246

  • Contact name

    Daniel Peckham

  • Contact email

    d.g.peckham@leeds.ac.uk

  • Sponsor organisation

    The Secretariat, University of Leeds

  • Duration of Study in the UK

    1 years, 0 months, 1 days

  • Research summary

    Cystic Fibrosis is a life-limiting inherited condition of the lungs, digestive, and reproductive systems. It affects 1 in 2500 people and the gene causing it is carried by 1 in 25 people on the UK. The Cystic Fibrosis Transmembrane Regulator (CFTR) protein channel is responsible for moving Chloride and Bicarbonate in and out of cells and with this Sodium and then water follows. In Cystic Fibrosis, the CFTR channel does not work properly leading to thick mucus secretions, which is particularly crucial to lung function. The thick, difficult to clear, mucus in the lungs leads to recurrent lung infections, damage to the lung tissue and end stage respiratory failure if left untreated.
    Recent advances in CF have led to the development of CFTR Modulator drugs that improve the function of this channel and cause stabilisation and improvement of lung function and chest symptoms.
    There has recently been a link between the CFTR protein, and the Epithelial Sodium Channel (ENac) established. This Sodium Channel causes an exaggerated inflammatory (swelling) response (NLRP-3 Inflammasone) without infective triggers being present.
    Further studies have shown that CFTR modulator drugs may also influence this pathway and reduce the inflammatory process in CF. This has been achieved by monitoring levels of pro-inflammatory markers (IL-18, IL-1b, caspase-1 activity and ASC speck release) from patients before and after starting these new therapies.
    This hypothesis has not been tested in children. With this study we aim to take blood samples from children with Cystic Fibrosis immediately before and at 3 months following the commencement of CFTR Modulator drugs. The blood tests would be taken alongside samples needed for routine care therefore there would be no need for additional painful procedures in these children.

  • REC name

    South Central - Oxford C Research Ethics Committee

  • REC reference

    22/SC/0344

  • Date of REC Opinion

    1 Sep 2022

  • REC opinion

    Favourable Opinion