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

• Sponsor: Nottingham University Hospitals NHS Trust (Other)
• Overall Status: Completed
• CT.gov ID: NCT03566550
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Actual Duration (Months): 5.6
• Patients Per Site Per Month: 4.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	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 Design

• Study Type: Observational
• Actual Enrollment: 25 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: Sep 4, 2018
• Actual Primary Completion Date: Feb 20, 2019
• Actual Study Completion Date: Feb 20, 2019

Arms and Interventions

Arm	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 [1 day of scanning]

   time taken after eating for ingested food to be identifiable in the caecum on MRI

Secondary Outcome Measures

1. Gastric Half Emptying Times [1 day of scanning]

   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)

2. Small Bowel Water Content (Corrected for Body Surface Area) [1 day of scanning]

   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)

3. Colonic Volume (Corrected for Body Surface Area) [1 day of scanning]

   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)

4. Gastrointestinal Symptoms [1 day of scanning]

   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.

Other Outcome Measures

1. T1 Relaxation Time of Ascending Colon Chyme [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 [1 day of scanning]

   A measure of fat content in chyme present in the ascending colon

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nottingham University Hospitals National Health Service Trust	Nottingham		United Kingdom	NG7 2UH

Sponsors and Collaborators

• Nottingham University Hospitals NHS Trust

Investigators

• Principal Investigator: Alan Smyth, Prof, University of Nottingham

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 1, 2018

More Information

Publications

None provided.

• Responsible Party: Nottingham University Hospitals NHS Trust
• ClinicalTrials.gov Identifier: NCT03566550
• Other Study ID Numbers: 18GA006
• First Posted: Jun 25, 2018
• Last Update Posted: Jul 21, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Recruitment Details

51 CF patients were eligible. CF patients were approached in order of their hospital attendance and the first 12 to provide written consent were enroled into the study. 13 declined to participate and 2 withdrew consent as they did not like the standardised meals or MRI. 12 CF patients and 12 controls completed the protocol without any adverse events. 1 further control was withdrawn and replaced as the participant was unable to complete the first standardised meal and the remaining 10 MRI scans.

Arm/Group Title	Cystic Fibrosis	Control
Arm/Group Description	people with cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals	people without cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals
Period Title: Overall Study
STARTED	12	13
COMPLETED	12	12
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Cystic Fibrosis	Control	Total
Arm/Group Description	people with cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals	people without cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	5 41.7%	5 41.7%	10 41.7%
Between 18 and 65 years	7 58.3%	7 58.3%	14 58.3%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 41.7%	5 41.7%	10 41.7%
Male	7 58.3%	7 58.3%	14 58.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	12 100%	12 100%	24 100%
Weight (kg) (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]	56	62	59
Height (cm) (cm) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cm]	166	166	166

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cystic Fibrosis	Control
Arm/Group Description	people with cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals	people without cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals
Measure Participants	12	12
Median (Inter-Quartile Range) [minutes]	330	210

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cystic Fibrosis, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Gastric Half Emptying Times
Description	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)
Time Frame	1 day of scanning

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cystic Fibrosis	Control
Arm/Group Description	people with cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals	people without cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals
Measure Participants	12	12
Median (Inter-Quartile Range) [minutes]	97	80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cystic Fibrosis, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Small Bowel Water Content (Corrected for Body Surface Area)
Description	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)
Time Frame	1 day of scanning

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cystic Fibrosis	Control
Arm/Group Description	people with cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals	people without cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals
Measure Participants	12	12
Median (Inter-Quartile Range) [L.min/m^2]	62	34

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cystic Fibrosis, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Colonic Volume (Corrected for Body Surface Area)
Description	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)
Time Frame	1 day of scanning

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cystic Fibrosis	Control
Arm/Group Description	people with cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals	people without cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals
Measure Participants	12	12
Median (Inter-Quartile Range) [L.min/m^2]	186	123

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cystic Fibrosis, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Gastrointestinal Symptoms
Description	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.
Time Frame	1 day of scanning

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cystic Fibrosis	Control
Arm/Group Description	people with cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals	people without cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals
Measure Participants	12	12
Median (Inter-Quartile Range) [CFAbd-Score units]	16	7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cystic Fibrosis, Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Other Pre-specified Outcome

Title	T1 Relaxation Time of Ascending Colon Chyme
Description	An approximate measure of water content in chyme present in the ascending colon
Time Frame	1 day of scanning

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Fat Fraction of the Ascending Colon Chyme
Description	A measure of fat content in chyme present in the ascending colon
Time Frame	1 day of scanning

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	1 day of MRI scanning
Arm/Group Title	Cystic Fibrosis		Control
Arm/Group Description	people with cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals		people without cystic fibrosis MRI scans: Repeated MRI scans imaging digestion of standard meals
All Cause Mortality
	Cystic Fibrosis		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Cystic Fibrosis		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Cystic Fibrosis		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.