Pseudo-obstruction Assessment With MRI (POM)

A Case-control Study of the Gastrointestinal Response to a Liquid Test Meal in Chronic Intestinal Pseudo-obstruction, Using Magnetic Resonance Imaging

This study will explore the potential for a standardized MRI scan after a liquid meal to be used in diagnosis of the rare but debilitating chronic intestinal pseudo-obstruction (CIPO).

Study Overview

• Status: Recruiting
• Conditions: Chronic Intestinal Pseudo-Obstruction
• Intervention / Treatment: Diagnostic test: MRI scans after a liquid meal

Detailed Description

People with chronic intestinal pseudo-obstruction (CIPO) have problems digesting their food properly, due to a problem in their gut nerves or muscle. There are not many good tests to assess how a patient's stomach and bowels are working. Finding out more is the first step in developing a standardized clinical test using MRI to provide a faster diagnosis than is currently possible. Magnetic resonance imaging (MRI) scans allow the investigators to see inside the abdomen. Scans are not painful or harmful and are therefore ideal for repeated measurements. By scanning participants both before and after a test drink the investigators can see exactly how their digestion is working.

The investigators are inviting 16 people who are at least 16 years old, 8 who have CIPO and 8 with chronic constipation, so the investigators can compare the images. Participants will come in for one half day of scanning. The investigators will take a total of 8 scans of their abdomens, every half hour. Participants will also fill in symptom questionnaires at every scan, for example if they feel bloated or have any abdominal pain. Each scan will take about 15 minutes and will require short breath holds. Participants will be able to get out of the scanner at any time point if they feel the need to.

Participants will arrive fasted in the morning and will receive a test drink (a milk-based drink used as an oral nutritional supplement) right after the first scan. All participants will be asked to pause some of their usual medication that has a direct influence on digestion for 24h before the scan day and during the ~4h of the study.

The primary outcome is peak small bowel motility, which the investigators hypothesize to be less active in people with CIPO. Other outcomes include gastric volume, small bowel water content and distribution, peak gastric motility, and gastrointestinal symptoms.

• Study Type: Observational
• Enrollment (Estimated): 16

Contacts and Locations

• Study Contact: Name: Giles Major, PhD; Phone Number: +44 115 8231035; Email: giles.major@nottingham.ac.uk
• Study Contact Backup: Name: Neele Dellschaft, PhD; Phone Number: +44 115 8467774; Email: neele.dellschaft@nottingham.ac.uk

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2RD
      • Recruiting
      • University of Nottingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cases will be recruited through Digestive Diseases clinical services across England; Controls will be recruited from the population of Nottingham.

Description

Inclusion Criteria:

• Ability to give informed consent
• Sufficient level of English language to understand study information and respond to symptom questionnaires
• CASES: a clinical diagnosis of primary or secondary Chronic Intestinal Pseudo-Obstruction, excluding adhesional obstruction. PICs will be asked to send clinical documentation that the diagnosis has been confirmed on crosssectional imaging.
• CONTROLS: a Chronic constipation disorder diagnosed according to Rome IV criteria for functional constipation, constipation-predominant irritable bowel syndrome or opioid-induced constipation (diagnostic criteria as listed in Lacy et al 2016)

Exclusion Criteria:

• Inability to tolerate 400 ml liquid challenge meal (oral or through established gastrostomy; according to self-assessment)
• Contra-indication to MRI scanning, such as metal implants, pacemaker etc
• Pregnancy declared by candidate (no formal testing)
• Inability to stop short-acting medications likely to alter small bowel motility, such as antiemetics, fast release opioids, laxatives, and anti-diarrhoeals, on the day before the study (24h before baseline scan; i.e. a total of circa 30h) as well as antibiotics for three days before the study. This only applies to long-term antibiotics commonly given for dysbiosis (small intestinal bacterial overgrowth). A short course of antibiotics given for acute infections will not be interrupted but the study day will be delayed until the course is finished. Patches, long acting formulations such as slow release medication or depot injection medication will be allowed to continue
• Inability to omit parenteral nutrition for 12 hours before the fasting MRI scan (~16h total)
• Medical comorbidity that means subject will not be able to undergo multiple scans e.g. severe respiratory disorder limiting time lying flat; severe musculoskeletal disorder limiting mobility
• Previous small bowel resection (excluding ileostomy, insertion of venting tube or percutaneous endoscopic gastrostomy, appendectomy or cholecystectomy). Patients who have had a colectomy for their CIPO will be eligible.
• Other gastrointestinal disorder likely to alter small bowel function e.g. uncontrolled coeliac disease, Crohn's disease. A diagnosis of small intestinal bacterial overgrowth will not be a reason for exclusion. PICs will be asked to supply information on resections and comorbidities for CIPO participants.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CIPO (case); MRI scan of gastrointestinal content and activity	Diagnostic test: MRI scans after a liquid meal; Participants will be scanned fasted, then receive a liquid meal, then be scanned every half hour, seven times
Chronic constipation (control); MRI scan of gastrointestinal content and activity	Diagnostic test: MRI scans after a liquid meal; Participants will be scanned fasted, then receive a liquid meal, then be scanned every half hour, seven times

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak small gut motility after a test liquid meal	Investigating whether people with CIPO have a lower peak small gut motility after a test drink than people who do not have CIPO. Small gut motility will be assessed with a standardised method on CineMRI, based on power spectrum analysis of voxel-signal changes with time (the outcome will be reported in arbitrary units). The primary outcome is peak small gut motility since a delay in motility (linked to one specific time point) would not be sufficient to explain the difference between CIPO and controls.	up to 3.5 hours after meal, measured every half hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric emptying rate (ml/min) after a test liquid meal	Investigating whether people with CIPO have slower gastric emptying after a test drink than people who do not have CIPO. The gastric emptying rate is determined by measuring the gastric volume every half hour after the standardised meal.	up to 3.5 hours after meal, measured every half hour
Small bowel water volume (ml) after a test liquid meal	Investigating whether people with CIPO have a greater volume of small bowel water after a test drink than people who do not have CIPO. Small bowel water content is determined from a heavily T2-weighted scan. The intensity threshold for free water will be set using each participant's spinal fluid, and only small bowel contents having an intensity equal to or greater than this value will be measured as small bowel free water volume.	up to 3.5 hours after meal, measured every half hour
Gastric motility after a test liquid meal	Investigating whether people with CIPO have a reduced gastric motility after a test drink than people who do not have CIPO. Gastric motility will be assessed with a standardised method on CineMRI, based on power spectrum analysis of voxel-signal changes with time (the outcome will be reported in arbitrary units).	up to 3.5 hours after meal, measured every half hour

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Northern Care Alliance NHS Foundation Trust; Cambridge University Hospitals NHS Foundation Trust; Barts & The London NHS Trust; Manchester University NHS Foundation Trust; Oxford University Hospitals NHS Trust; London North West Healthcare NHS Trust; Pseudo-Obstruction Research Trust
• Investigators: Principal Investigator: Giles Major, PhD, University of Nottingham

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2020
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: November 22, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Obstruction; Ileus; Intestinal Pseudo-Obstruction
• Other Study ID Numbers: 19069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymised IPD may be available for sharing as part of collaborative data pooling but will not automatically be published as open source due to the possibility of identification through meta-data in a rare disease.

Drug and device information, study documents

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