Gut Imaging for Function & Transit in CF - GIFT-CF 3

NCT04618185 | Completed

• 1 other identifier: 20CS036
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

An observational study of patients with cystic fibrosis (CF) starting treatment with Kaftrio (Elexacaftor / Tezacaftor / Ivacaftor) as part of routine clinical care, following EMA licensing (approved end of Aug 2020).

• Patients with CF who are p.Phe508del homozygotes will already be receiving the less effective CFTR modulator drug Symkevi (Tezacaftor / Ivacaftor) and will switch to KaftrioTM.
• Patients who are who are compound heterozygotes with at least 1 copy of p.Phe508del currently have access to no effective CFTR modulator and will be starting a CFTR modulator (Kaftrio) for the first time. Participants attend a study visit before Kaftrio treatment commences, followed by visits at 12 and 24 weeks after starting treatment. At each visit they will be scanned before and after standardised meals in the morning and mid-day (11 scans in total over 6 hours). No intravenous contrast or bowel preparation will be used. Participants will complete questionnaires on gastrointestinal symptoms as well as providing stool and sputum samples for assessment of microbiome and stool for inflammatory mediators and pancreatic function (elastase). \*\*Following an extension, participants had a further visit at 76 weeks post starting Kaftrio, updated in detailed description\*\*

Conditions

Cystic Fibrosis

Keywords

Magnetic Resonance Imaging; Oro-caecal transit time; Small bowel water; Colonic volume; Gastrointestinal symptoms; Stool and sputum microbiome; CFTR modulator

Outcome Measures

Primary Outcomes (1)

• Difference in oro-caecal transit time (OCTT) in minutes at baseline and 24 weeks and baseline and 76 weeks

  the time when the test meal is first detectable in the caecum

  4 days of scanning

Secondary Outcomes (13)

• Small bowel water content (SBWC) area under the curve (AUC), corrected for body surface area, measured in L.min/m^2 between 0 and 360 minutes at baseline, 12 weeks, 24 weeks and 76 weeks

  4 days of scanning

• Change in SBWC between 240 and 300 minutes (delta DTI) at baseline, 12 weeks, 24 weeks and 76 weeks

  4 days of scanning

• Colonic volume area under the curve (AUC), corrected for body surface area at baseline, 12 weeks, 24 weeks and 76 weeks

  4 days of scanning

• Stool calprotectin at baseline, 12 weeks, 24 weeks and 76 weeks

  4 days of scanning

• Stool and sputum microbiome at baseline, 12 weeks, 24 weeks and 76 weeks

  4 days of scanning

Other Outcomes (5)

• T1 relaxation of ascending colon chyme at baseline, 12 weeks, 24 weeks and 76 weeks

  4 days of scanning

• T2* of the terminal ileum

  4 days of scanning

• Terminal ileum diameter at baseline, 12 weeks, 24 weeks and 76 weeks

  4 days of scanning

Study Arms (2)

p.Phe508del homozygous genotype

People with CF with 2 copies of p.Phe508del and previously eligible for Symkevi (Tezacaftor/Ivacaftor)

Diagnostic Test: Magnetic Resonance Imaging (MRI)

p.Phe508del heterozygous genotype

People with CF with 1 copy of p.Phe508del and not previously eligible for any CFTR modulator

Diagnostic Test: Magnetic Resonance Imaging (MRI)

Interventions

Magnetic Resonance Imaging (MRI) DIAGNOSTIC_TEST

MRI to study gut function and transit without the risk of exposure to ionising radiation.

p.Phe508del heterozygous genotype; p.Phe508del homozygous genotype

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

All CF patients who receive care by Nottingham University Hospitals NHS Trust and are eligible for the study will be approached by their usual care team.

You may qualify if:

• Age 12 - 60 years
• Capacity to consent, or to understand the requirements of the study where parental consent is needed.
• Confirmed diagnosis of CF, either by sweat test or genetic testing.
• Genotype homozygous p.Phe508del or compound heterozygous with at least 1 copy of p.Phe508del.
• Eligible for KaftrioTM (Elexacaftor / Tezacaftor / Ivacaftor) treatment but not yet commenced Kaftrio treatment as part of routine care.

You may not qualify if:

• Contra-indication to MRI scanning, such as embedded metal, pacemaker.
• FEV1 \< 40% (% predicted using Global Lung Initiative values)
• Unable to stop medications directly prescribed to alter bowel habit, such as laxatives of anti-diarrhoeals, on the study day
• Previous resection of small bowel \>20cm in length
• Intestinal stoma
• Diagnosis of inflammatory bowel disease or coeliac disease, confirmed by biopsy
• Gastrointestinal malignancy
• Unable to comply with dietary restrictions required for the study
• Pregnancy - tests are available at the SPMIC if participants are unsure
• Unable to speak or understand English

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead
• Manchester Metropolitan University: collaborator
• Vertex Pharmaceuticals Incorporated: collaborator

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Stool and sputum samples frozen pre-analysis

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Magnetic Resonance Imaging

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)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Alan Smyth

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: November 5, 2020
• Study Start: October 21, 2020
• Primary Completion: June 28, 2023
• Study Completion: June 28, 2023
• Last Updated: May 23, 2024

Record last verified: 2024-05

Locations

GB (1)