A Case-Control, Observational Study of the Postprandial Changes in Magnetic Resonance Imaging Parameters of Gastrointestinal Function and Transit in People With Cystic Fibrosis
Conditions: Cystic Fibrosis
Sponsor: Nottingham University Hospitals NHS Trust

 
 
 
University of Nottingham 
Gut Imaging for 
Function & Transit 
in Cystic Fibrosis 
Study 1 
Study protocol 1 September 2018, NCT03566550 
 

Brief Summary 
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. 
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 score their abdominal pain, bloating and flatulence symptoms on a Likert scale. 
In between scans, participants will have access to a lounge with wi-fi 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 Design 
Study Type: Observational 
Actual Enrollment: 24 participants 
Observational Model: 
Case-Control 
Time Perspective: Cross-Sectional 
Official Title: 
A Case-Control, Observational Study of the Postprandial 
Changes in Magnetic Resonance Imaging Parameters of Gastrointestinal Function 
and Transit in People With Cystic Fibrosis 
Actual Study Start Date: September 4, 2018 
Actual Primary Completion Date: 
February 20, 2019 

Actual Study Completion Date: February 20, 2019 
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 
 
Outcome Measures 
Primary Outcome Measures: 
1. orocaecal transit time [ Time Frame: 1 day of scanning ] - time taken after 
eating for ingested food to be identifiable in 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 speed of gastric emptying 
2. small bowel water content (corrected for body surface area) [ Time Frame: 1 
day of scanning ] - volume of water content in small bowel representing 
secretions 
3. colonic volume (corrected for body surface area) [ 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 as measured by questionnaires to monitor relationship with 
outcomes measured by MRI 
 
Other Outcome Measures: 
1. T1 relaxation time of ascending colon chyme [ Time Frame: 1 day of scanning 
] - An approximate measure of water content in chyme present in the 
ascending colon 
2. Fat fraction of the ascending colon chyme [ Time Frame: 1 day of scanning ] - 
A measure of fat content in chyme present in the ascending colon 
Eligibility Criteria 
Ages Eligible for Study:   12 Years to 40 Years   (Child, Adult) 
Sexes Eligible for Study:   
All 
Accepts Healthy Volunteers:   Yes 
Sampling Method:   
Non-Probability Sample 
Study Population 
Nottingham and surrounding towns 
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 intestinal 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 

 
 
Statistical analysis plan 
Data will be summarised through descriptive statistics. Differences between Patient 
and Control data will be tested using non-parametric methods. The software used 
will be GraphPad Prism version 7.0 or later, or SPSS version 21 or later, under 
licence to the University of Nottingham. 
The primary and secondary outcomes will be compared firstly between CF patients 
and the non-CF controls using a t-test (for normally distributed variables) or a Mann-
Whitney U test (for non-normally distributed data). We will then explore the 
association between the results of the symptom questionnaires and the MRI findings. 
We will compare MRI parameters such as OCTT, small bowel water and colonic 
volume against both the total CF Abdomen-Score and against the score for 
individual domains. An example of the latter would be comparing OCTT with the 
domains of “constipation” & “too much time spent on the toilet” from the CF 
Abdomen-score. We will compare these using a t-test or Mann Whitney U test, 
where the MRI parameter is a binary or categorical variable, and Pearson or 
Spearman’s correlation coefficient for continuous MRI parameters. 
Where data is missing, through participant withdrawal or technical failure (e.g. 
scanner breakdown), an imputed value will be assigned which will be the median 
value for that parameter of other participants in the participant group (Patient/ 
Control) at that time point.