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NCT07402434

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

Sponsor: Royal Brompton & Harefield NHS Foundation Trust

View on ClinicalTrials.gov

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.

Official title: Advanced Diagnostic Validation and Novel Clinical Evaluation Across the CFTR Spectrum (ADVANCE-CFTR): a Prospective Study of CFTR Functional Assays, Including Rectal Organoids, to Improve the Accuracy of Diagnosing Cystic Fibrosis.

Key Details

Gender

All

Age Range

16 Years - Any

Study Type

OBSERVATIONAL

Enrollment

Start Date

2026-02-02

Completion Date

2028-09-01

Last Updated

2026-02-17

Healthy Volunteers

Yes

Conditions

Cystic Fibrosis (CF)CFTR-related Disorders

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.

Inclusion Criteria: Group A: Difficult Cystic Fibrosis Diagnosis Cohort Inclusion criteria: 1. Patients with difficult-to-diagnose CF\* 2. Adults (≥16y) 3. Willing to undergo rectal biopsy 4. Able to comply with the study * Definition: Non-diagnostic first line CFTR testing (individuals who do not fulfil CF diagnostic criteria \[2 CF-causing CFTR variants and/or sweat chloride concentration ≥60 mmol/L\]). Of note, there are some individuals with \<2 CF-causing CFTR variants after extended CFTR genetic analysis but with a SCC \>60mmol/L. Expansion of the patient pool to include these is permissible. Group B: Cystic Fibrosis Patient Cohort Inclusion criteria: 1. Patients with confirmed Cystic Fibrosis 2. Adults (≥16y) 3. Willing to undergo rectal biopsy for this study 4. Able to comply with the study Group C: Non-Cystic Fibrosis Patient Cohort Inclusion criteria: 1. Patients without Cystic Fibrosis or CFTR-related disorder 2. Adults (≥16y) 3. Willing to undergo rectal biopsy for this study (if undergoing a lower GI endoscopy for other purposes) 4. Able to comply with the study Exclusion Criteria: Group A: Difficult Cystic Fibrosis Diagnosis Cohort Exclusion criteria: 1. Contra-indication to rectal biopsy (e.g. significant bleeding diathesis) 2. History of lung transplantation 3. Receiving CFTR modulator treatment 4. Current participation (or participation within one month of enrolment) in a clinical trial of an investigational medicinal product which affects CFTR function (e.g. CFTR modulators, genetic therapies) 5. Female who is pregnant or breastfeeding 6. Unable to provide informed consent Group B: Cystic Fibrosis Patient Cohort Exclusion criteria: 1. Contra-indication to rectal biopsy (e.g. significant bleeding diathesis) 2. Current participation (or participation within one month of enrolment) in a clinical trial of an investigational medicinal product which affects CFTR function (e.g. CFTR modulators, genetic therapies) 3. Female who is pregnant or breastfeeding 4. Unable to provide informed consent 5. Exclude all subjects where diagnosis of CF is in doubt Group C: Non-Cystic Fibrosis Patient Cohort Exclusion criteria: 1. Contra-indication to rectal biopsy (e.g. significant bleeding diathesis) 2. Female who is pregnant or breastfeeding 3. Unable to provide informed consent

Locations (1)

Royal Brompton Hospital

London, United Kingdom