Gut Imaging for Function & Transit in Cystic Fibrosis Study 1 (GIFT-CF1)

A Case-Control, Observational Study of the Postprandial Changes in Magnetic Resonance Imaging Parameters of Gastrointestinal Function and Transit in People With Cystic Fibrosis

Many people with Cystic Fibrosis (CF) are troubled by symptoms from their stomach and bowels: their gastrointestinal (GI) tract. Symptoms affect quality of life and can also reduce people's ability to digest enough calories to remain healthy, leaving them undernourished and less able to deal with other health problems such as infection.

Clinical tests to assess bowel function are limited. Many tests involve inserting a sensor or camera into the bowel, so they are not suitable for long periods, and can be uncomfortable. In Nottingham the investigators have developed imaging scans which can assess how someone's digestion works without any invasive device. The type of scanning the investigators use is called Magnetic Resonance Imaging, or MRI.

The purpose of this study is to see if those scanning methods can be used in people with CF to understand their digestion and any problems they have.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Diagnostic test: MRI scans

Detailed Description

This is a small pilot study to establish that differences in digestion between people with and without CF can be quantified by repeated MR scans in fasted participants in response to standardised meals.

Participants will complete questionnaires on gastrointestinal function and symptoms: the PAC-SYM questionnaire, validated to assess symptom burden in adults with chronic constipation; and the CF abdomen questionnaire, developed in German for use in young people and adults with cystic fibrosis.

After this, participants only need to attend one study day at the Sir Peter Mansfield Imaging Centre. On this day they will be asked to withhold any medicines specifically targeted to alter bowel habit. This shall include laxatives but not enzyme replacement therapy. They should attend on the study day having fasted since waking, other than water for essential medicines.

They will have their first MRI scan fasted. After the scan they will eat a standard test meal, and be scanned again first at half hour, then hour intervals until six hours after the first meal. The final scan will constitute the end of the study for each participant. Each session in the MRI scanner will last around 15 minutes. After each scan they will complete a validated rating scale for any current symptoms: the Gastrointestinal Symptom Rating Scale (GSRS).In between scans, participants will have access to a lounge with wifi and a television.

Infection control requirements mean that the investigators are unable to scan more than one patient with CF on a single day. Patient scans will alternate with those of a Control participant. The investigators will aim to frequency match Controls with Patients for age and gender.

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals National Health Service Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Nottingham and surrounding towns

Description

Inclusion Criteria:

• Age 12 - 40 years
• Capacity to consent, or to understand the requirements of the study where parental consent is needed
• PATIENTS: confirmed diagnosis of Cystic Fibrosis, either by sweat test or genetic testing; to reduce heterogeneity, we will only enrol homozygous CF patients with the most common CFTR mutation, p.Phe508del
• CONTROLS: no clinical evidence or suspicion of Cystic Fibrosis

Exclusion Criteria:• Measurement of Forced Expiratory Volume in 1 second (FEV1) of <40% predicted using Global Lung Initiative criteria, according to clinical records

• Contra-indication to MRI scanning, such as embedded metal, pacemaker
• Unable to stop medications directly prescribed to alter bowel habit, such as laxatives of anti-diarrhoeals, on the study day
• Previous resection of any part of the gastro-intestinal tract apart from appendicectomy or cholecystectomy. Surgical relief of distal ileal obstruction syndrome or neonatal ileus 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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CF; people with cystic fibrosis	Diagnostic test: MRI scans; Repeated MRI scans imaging digestion of standard meals
Control; people without cystic fibrosis	Diagnostic test: MRI scans; Repeated MRI scans imaging digestion of standard meals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Orocaecal Transit Time	time taken after eating for ingested food to be identifiable in the caecum on MRI	1 day of scanning

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric Half Emptying Times	volume of stomach at each time point of digestion to measure speed of gastric emptying (time taken for half the gastric contents to be emptied)	1 day of scanning
Small Bowel Water Content (Corrected for Body Surface Area)	volume of water content in small bowel representing secretions (area under the curve - timepoints at baseline then 0,30,60,90,120,150,180,240,300,360 minutes)	1 day of scanning
Colonic Volume (Corrected for Body Surface Area)	volume of colon representing ease of chyme passage through colon (area under the curve - timepoints at baseline then 0,30,60,90,120,150,180,240,300,360 minutes)	1 day of scanning
Gastrointestinal Symptoms	gastrointestinal symptoms as measured by questionnaires to monitor relationship with outcomes measured by MRI. Scale of the CFAbd-score ranges from 0-100. A low score indicates fewer gastrointestinal symptoms whilst a higher score indicates more severe and frequent gastrointestinal symptoms.	1 day of scanning

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
T1 Relaxation Time of Ascending Colon Chyme	An approximate measure of water content in chyme present in the ascending colon	1 day of scanning
Fat Fraction of the Ascending Colon Chyme	A measure of fat content in chyme present in the ascending colon	1 day of scanning

Collaborators and Investigators

• Sponsor: Nottingham University Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2018
• Primary Completion (Actual): February 20, 2019
• Study Completion (Actual): February 20, 2019

Study Registration Dates

• First Submitted: June 12, 2018
• First Submitted That Met QC Criteria: June 12, 2018
• First Posted (Actual): June 25, 2018

Study Record Updates

• Last Update Posted (Actual): July 21, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 18GA006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual participant data outside the research team at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No