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

NCT ID: NCT04618185

Last Updated: 2024-05-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

24 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-10-21

Study Completion Date

2023-06-28

Brief Summary

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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\*\*

Detailed Description

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This is an observational study to observe the effects of Kaftrio (Elexacaftor / Tezacaftor / Ivacaftor) on the gut in people with CF.

Participants will attend 4 times, following an extension (pre-Kaftrio, at 12 weeks of Kaftrio at 24 weeks of Kaftrio and 76 weeks of Kaftrio) for MRI scanning at the Sir Peter Mansfield Imaging Centre, after an overnight fast. On this day, participants will be asked to withhold any medicines directly altering bowel habit such as laxatives. They will continue to take pancreatic enzyme replacement therapy and other medications for CF.

The Investigators will use the same MRI protocol as described in GIFT-CF (NCT03566550 and NCT04006873). Participants will have their first MRI scan fasted. After the first scan, they will eat a first standardised meal . They will then have 7 MRI scans at half hourly intervals and 3 MRI scans at hourly intervals. Participants will be given a second standardised meal after their ninth MRI scan. Each MRI scan will last approximately 15 minutes. After each MRI scan, participants will complete a validated gastrointestinal symptom questionnaire (Gastrointestinal Symptom Rating Scale). In between scans, participants will have access to an adjacent room with Wifi and television access.

They will also complete gut symptom questionnaires relating to the preceding 2 weeks and a 3 day food diary. They will also provide a sputum and stool sample.

Infection control requirements mean that only 1 participant will attend for MRI scanning per day. Extra COVID-19 precautions will also be taken throughout scan days.

\*\*\*Please note, due to the timing of EMA approval for Kaftrio and ethics approval for the study granted on 21st Ocober 2020, the clinicaltrials.gov registration was created on 21st October 2020 and approved by the clinicaltrials.gov PRS team on 4th November 2020.\*\*\*

Conditions

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Cystic Fibrosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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p.Phe508del homozygous genotype

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

Magnetic Resonance Imaging (MRI)

Intervention Type DIAGNOSTIC_TEST

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

p.Phe508del heterozygous genotype

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

Magnetic Resonance Imaging (MRI)

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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Magnetic Resonance Imaging (MRI)

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

12 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Manchester Metropolitan University

OTHER

Sponsor Role collaborator

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role collaborator

Nottingham University Hospitals NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alan Smyth

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Locations

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Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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20CS036

Identifier Type: -

Identifier Source: org_study_id

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