A Prospective Study of Advanced Diagnostics in People With an Unclear Diagnosis of Cystic Fibrosis

Summary

Sometimes it is very difficult to tell if someone has cystic fibrosis (CF), especially when they have rare CF genes. Without this certainty, they are unlikely to get the correct treatment so their health may be affected. More accurate ways to test for CF are therefore needed in this situation. The aim of this study is to develop a more accurate test using what are called "organoids" or "mini organs." Organoids are grown in the laboratory from a small piece of gut tissue. As they have the person's exact genes, they can show if the CF gene ("CFTR") is working correctly or not and thus if the person has CF. The investigators will compare the organoid response with the current more established tests, such as the sweat test and CF genetics, and other recognised specialist tests called nasal potential difference (NPD) and intestinal current measurement (ICM). The gut tissue is usually taken by a quick, relatively painless, outpatient procedure (rectal biopsy). The additional benefit of organoids is that they can also help us to work out the best treatment for that individual by testing how well the gut tissue responds to different drugs in the laboratory. The investigators wish to carry out this research to prove that gut organoids are a better way to test for CF in this situation. The goal will be to diagnose people faster and for them to get better treatment quicker, both key for leading a longer and healthier life.

Conditions

• CFTR-related Disorders
• Cystic Fibrosis (CF)

Interventions

PROCEDURE

Rectal Biopsy

Rectal biopsy sampling will be performed using either forceps or a suction device according to the method of Vonk et al (2020). Rectal biopsies will be obtained by trained and competent personnel in an appropriate setting, patients recruited will be fully informed and will have provided written consent. Once biopsy samples have been taken the resulting tissue will be processed, stored and transported using established laboratory protocols. The rectal tissue collected will be used to perform intestinal current measurements and create organoids or 'mini-organs' to allow CFTR protein function to be further characterised.

PROCEDURE

Rectal biopsy taken opportunistically during endoscopy procedure for other reasons.

Rectal Biopsy tissue samples will be taken opportunistically for this patient cohort who are undergoing an endoscopy for other reasons. Rectal biopsies will be obtained by trained and competent personnel in an appropriate setting, patients recruited will be fully informed and will have provided written consent. The rectal tissue collected will be used to perform intestinal current measurements and create organoids or 'mini-organs' to allow CFTR protein function to be further characterised.

GENETIC

Blood test for CFTR Genotyping

Blood test for CFTR genotyping will be taken for Group C patients to ensure these patients are 'healthy controls' and that they do not have any CFTR gene variants associated with CF.

Sponsors & Collaborators

• King's College London

  collaborator OTHER

• UMC Utrecht

  collaborator OTHER

• Imperial College London

  collaborator OTHER

• Royal Brompton & Harefield NHS Foundation Trust

  lead OTHER

Principal Investigators

• Nicholas J Simmonds · Royal Brompton Hospital and Imperial College London

Eligibility

Min Age

16 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-02-02

Primary Completion

2028-06-01

Completion

2028-09-01

Countries

• United Kingdom

Study Locations