Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Gut Imaging for Function & Transit in Cystic Fibrosis Study 2 (GIFT-CF2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04006873
Recruitment Status : Not yet recruiting
First Posted : July 3, 2019
Last Update Posted : July 9, 2019
Sponsor:
Collaborators:
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation
Cystic Fibrosis Trust
University of Nottingham
Nottingham University Hospitals Charity
Information provided by (Responsible Party):
Nottingham University Hospitals NHS Trust

Brief Summary:

People with Cystic Fibrosis (CF) have problems digesting their food properly. More than 8 in 10 people with CF must take medication to assist their digestion. In spite of this, complications such as bowel blockage occur.

Finding out how already licenced drugs for CF work in the gut is the first step in repurposing medications. Tezacaftor/Ivacaftor with Ivacaftor is a drug combination which corrects the basic defect in CF an has shown improvements on lung function.

The purpose of this study is to evaluate, using Magnetic Resonance Imaging (MRI) and patient-reported outcomes, whether Tezacaftor/Ivacaftor with Ivacaftor has an effect on improving gastrointestinal problems in CF.


Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Tezacaftor/Ivacaftor + Ivacaftor Drug: Placebo oral tablet Phase 2

Detailed Description:

This is a small pilot study to compare the effects of active drug (Tezacaftor/Ivacaftor with Ivacaftor) on the gut in people with CF.

Participants will be randomised to take active drug or matched placebo for 28 days then switch to the alternate drug after a 28 day washout period. Before participants commence treatment, they will have blood pressure and baseline blood tests.

Participants will attend once per treatment period 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). 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.

During the day, participants will have their lung function, blood pressure and blood tests taken. They will also provide a sputum and stool sample.

Infection control requirements mean that only 1 participant will attend for MRI scanning per day.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Official Title: A Randomised Crossover Pilot Study of the Effects of Tezacaftor/Ivacaftor and Ivacaftor on Gastrointestinal Function Using Magnetic Resonance Imaging Parameters in People With Cystic Fibrosis
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arm Intervention/treatment
Active Comparator: Tezacaftor/Ivacaftor in combination with Ivacaftor

A film-coated tablet containing 100mg tezacaftor and 150mg ivacaftor will be taken in the morning.

A film-coated tablet containing 150mg ivacaftor will be taken in the evening.

Participants will take these tablets for 28 days.

All tablets are licensed for use in the EU.

Drug: Tezacaftor/Ivacaftor + Ivacaftor
As per description in arms.
Other Names:
  • VX-661 100mg / VX-770 150mg active tablets
  • VX-770 150mg active tablets

Placebo Comparator: Placebo
A visually matched placebo to the active drugs will be taken in the morning and in the evening for 28 days.
Drug: Placebo oral tablet
As per description in arms
Other Name: Matching placebo tablets




Primary Outcome Measures :
  1. Oro-caecal Transit Time [ Time Frame: 1 day of scanning ]
    Time taken after eating for ingested food to be identifiable at the caecum on MRI


Secondary Outcome Measures :
  1. Gastric volume [ Time Frame: 1 day of scanning ]
    Volume of stomach at each time point of digestion to measure gastric emptying time

  2. Small bowel water content [ Time Frame: 1 day of scanning ]
    Volume of water content in small bowel representing secretions

  3. Colonic volume [ Time Frame: 1 day of scanning ]
    Volume of colon representing ease of chyme passage through colon

  4. Gastrointestinal symptoms [ Time Frame: 1 day of scanning ]
    Gastrointestinal symptoms measured by patient reported outcomes to monitor relationships with outcomes measure by MRI


Other Outcome Measures:
  1. Sigmoid colon volume [ Time Frame: 1 day of scanning ]
    Volume of sigmoid colon

  2. T1 relaxation of ascending colon chyme [ Time Frame: 1 day of scanning ]
    An approximate measure of water content in chyme present in the ascending colon

  3. Fat fraction of ascending colon chyme [ Time Frame: 1 day of scanning ]
    A measure of fat content in chyme present in the ascending colon

  4. Faecal elastase [ Time Frame: 1 day ]
    A measure of elastase in stool to evaluate pancreatic function

  5. Sputum and faecal microbiome [ Time Frame: 1 day ]
    A measure of microbiome in sputum and stool

  6. Faecal calprotectin [ Time Frame: 1 day ]
    A measure of intestinal inflammation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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. Tezacaftor/Ivacaftor is indicated only for patients homozygous for the commonest CF mutation - p.Phe508del and so we will enrol only CF patients with this genotype

Exclusion Criteria:

  • currently taking CFTR modulator drug
  • Contra-indication to use of Tezacaftor/Ivacaftor
  • Measurement of FEV1 <40% predicted using Global Lung Initiative criteria, according to clinical records, as participants will be required to perform a series of 10 second breathholds throughout MRI scanning
  • Contra-indication to MRI scanning, such as embedded metal, pacemaker.
  • Pregnancy
  • Unable to stop medications directly prescribed to alter bowel habit, such as laxatives or anti-diarrhoeals, on the study day
  • Previous resection of any part of the gastrointestinal tract apart from appendicectomy or cholecystectomy. Surgical relief of meconium ileus or DIOS will be permitted unless clinical records show excision of intestine >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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04006873


Contacts
Layout table for location contacts
Contact: Christabella Ng, Dr 0115 8231220 christabella.ng@nottingham.ac.uk
Contact: Giles Major, Dr 0115 9657348 giles.major@nottingham.ac.uk

Locations
Layout table for location information
United Kingdom
Nottingham University Hospitals NHS Trust Not yet recruiting
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
Nottingham University Hospitals NHS Trust
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation
Cystic Fibrosis Trust
University of Nottingham
Nottingham University Hospitals Charity
Investigators
Layout table for investigator information
Principal Investigator: Alan Smyth, Prof University of Nottingham
Principal Investigator: Giles Major, Dr University of Nottingham

Layout table for additonal information
Responsible Party: Nottingham University Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT04006873     History of Changes
Other Study ID Numbers: 18RM039
First Posted: July 3, 2019    Key Record Dates
Last Update Posted: July 9, 2019
Last Verified: July 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Layout table for MeSH terms
Molecular Mechanisms of Pharmacological Action
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators