Small and Large Bowel Transit Tests Using MRI (Study 1)

Irritable Bowel Syndrome Clinical Trial

Official title:

Optimising Measurement of Small and Large Bowel Transit During MRI Scanning and Characterising IBS Subtypes and Their Response to Stress Using MRI (Study 1)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01534507
• Other study ID #: 11038
• Secondary ID: 11/EM/0245 (Stud
• Status: Completed
• Phase: N/A
• First received: February 13, 2012
• Last updated: August 12, 2014
• Start date: November 2011
• Est. completion date: August 2014

Study information

• Verified date: August 2014
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial Summary

Irritable bowel syndrome, (IBS) is a common functional disorder of the gut that can be quite disabling to patients. The most common symptoms of IBS are abdominal pain or discomfort along with erratic changes in bowel habit of diarrhoea, constipation or a mixture of the two (referred to as IBS subtypes). Despite much research efforts to further understand the pathophysiology of IBS; as yet no specific biomarkers/definitive measurements have been identified that can be use to aid the diagnosis and reduce the need for unnecessary, unpleasant and expensive tests.

Evidence shows that anxiety plays a part in IBS and can speed up transit time in the small bowel. In this study, the investigators hypothesise that since anxiety is a common feature of IBS, then fast small bowel transit is likely to be found in all subtypes of IBS and the difference in stool frequency and consistency in IBS subgroups are therefore likely to reflect differences in colonic function. The investigator wish to test this by measuring both small and large bowel transit times using Magnetic Resonance Imaging (MRI) and validate the results of the MRI with two methods currently used in clinical practice -The previously validated lactose-C13 Ureide breath test (for small bowel transit) and the standard radio-opaque pellet method to assess the whole gut transit (WGT) time.

Description:

The investigator has 2 main parts in this study i.e. Study 1 and Study 2.

As part of study 1, the investigator would like to recruit up to 5 healthy volunteers as a pilot study to optimise measurement and analysis of the Lactose-C13 Ureide breath test along with MRI scannings at regular intervals.

Following from this, the investigator would like assess the feasibility and reproducibility of using MRI imaging to assess gastrointestinal transit. The investigator would like to recruit 21 healthy volunteers to measure orocaecal transit time (OCTT) and whole gut transit(WGT)using the conventional method of Lactose-C13 Ureide breath test for OCTT and the Metcalf method using standard radio-opaque pellet method for WGT and compare them will MRI imaging. Once this has been analysed and the best method for each OCTT and WGT have been decided, these methods would be applied in Study 2.

In study 2, the investigator would like to recruit 30 healthy volunteers, 30 patients with diarrhoea predominantly Irritable Bowel Syndrome, 30 patients with constipation predominantly Irritable Bowel Syndrome and 30 patients with Mixed irritable Bowel Syndrome. The best methods from study 1 for OCTT and WGT will be applied here to assess gastrointestinal transit on these subjects. Based on the first study, the best method to assess OCTT is the Lactose-C13 Ureide breath test and for the WGT, the best method is the MRI marker capsules. Participants will need to fill in questionnaires to assess their stress levels and to fill in symptom questionnaires during the study day.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Study 1

Inclusion Criteria

• 26 healthy volunteer

• Age 18-75 years old

• Non-smoker

• Able to give informed consent

Exclusion Criteria

• Lactose intolerant

• Any history of gastrointestinal surgery on the small bowel (excluding appendicectomy)

• Pregnancy

• contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury alcohol dependence

• serious concomitant illness as judged by the investigators

• use of drugs known to alter GI motility including opiates, anti-depressants, selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists during or in the 2 weeks prior to the test

• inability to lie flat or exceed scanner limits of weight >120kg or abdominal circumference >99cm ; BMI <18 and >30 kg/m2

• Poor command of English language

• Participation of any medical trials for the past 3 months

Study 2:

120 participants consisting of: 30 patients with diarrhoea predominant IBS according to Rome III criteria 30 patients with constipation predominant IBS according to Rome III criteria 30 patients with mixed type IBS according to Rome III criteria 30 healthy volunteers age and sex matched controls

Inclusion criteria

• Meet the Rome III criteria and the IBS subtypes

• Age 18-75 years old

• Able to give informed consent

• Subjects will undergo a limited screening medical. They will also complete a MRI - safety questionnaire and be given an information sheet

• Able to give informed consent

• Subjects will undergo screening medical questionnaire. They will also complete a MRI safety questionnaire and be given an information sheet

Exclusion Criteria

• Any history of gastrointestinal surgery on the small bowel (excluding appendicectomy)

• Pregnancy

• contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury

• alcohol dependence

• serious concomitant illness as judged by the investigators

• use of drugs known to alter GI motility including opiates, , monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists during or in the 2 weeks prior to the test

• Selective serotonin reuptake inhibitors or low dose tricyclic antidepressants will be recorded but will not be an exclusion

• No recent antibiotic treatment past 2 weeks

• inability to lie flat or exceed scanner limits of weight >120kg or abdominal circumference >99cm; BMI <18 and >30 kg/m2

• Poor command of English language

• Participation of any medical trials for the past 3 months

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Irritable Bowel Syndrome

Locations

Country	Name	City	State
United Kingdom	University of Nottingham	Nottingham	Notts

Sponsors (1)

Lead Sponsor	Collaborator
University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

Chaddock G, Lam C, Hoad CL, Costigan C, Cox EF, Placidi E, Thexton I, Wright J, Blackshaw PE, Perkins AC, Marciani L, Gowland PA, Spiller RC. Novel MRI tests of orocecal transit time and whole gut transit time: studies in normal subjects. Neurogastroenter — View Citation

Metcalf AM, Phillips SF, Zinsmeister AR, MacCarty RL, Beart RW, Wolff BG. Simplified assessment of segmental colonic transit. Gastroenterology. 1987 Jan;92(1):40-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study 1:Correlation between mean orocaecal transit time as assessed by MRI and lactose C13-ureide	MRI:Orocaecal transit time (OCTT) can be measured by the first scan showing arrival of the head of a meal in the ascending colon Lactose C13-Ureide breath test:Orocaecal transit time will be taken as the time at which a significant increase from background in breath 13C was seen.	9 hours	No
Primary	Study 1: Correlation between colonic transit as assessed by from the geometric centre of the PTFE capsule at time 24 and 48 hours and Metcalf Radio-opaque marker method	Colonic transit using MRI will be measure by assessing the geometric centre position in colon/small bowel.; Whole gut transit time using the Metcalf method of Radio-opaque Marker method would be estimated by counting the number of pellets remaining in the colon in an abdominal x-ray taken in day 4 * 1.2	72 hours	No
Primary	Study 2: Fasting small bowel water content	Fasting small bowel water content (SBWC) in the 3 subgroups of Irritable Bowel Syndrome (IBS) compared to healthy controls	1 hour	No
Secondary	Study 1:To assess reproducibility of the using MRI for orocaecal transit time and colonic transit time	In study 1, the orocaecal transit time and colonic transit time would be repeated twice with a week break in between to assess reproducibility of the MRI.	21 days	No
Secondary	Study 2: Orocaecal transit time using lactose C13-ureide	Orocaecal transit time in the 3 subgroups of IBS versus healthy control using the best method from study 1 which is the lactose C13-Ureide breath test	9 hours	No
Secondary	Study 2: Area under the curve (AUC) post prandial SBWC		9 hours	No
Secondary	Study 2: Ascending colon water content (ACWC) and colonic water index (CWI)		9 hours	No
Secondary	Study 2: Colonic volumes both fasting and post prandial (divided into ascending transverse and descending colon)		9 hours	No
Secondary	Study 2: Whole gut transit time assess by MRI marker capsule from study 1	The best method to assess the whole gut transit time based on study 1 was the use of the MRI marker capsule at time 24hours	24 hours	No
Secondary	Study 2: Correlation between the Hospital Anxiety & Depression Scale (HADS) and other measures of anxiety and stress score and (a) Oro-caecal transit time and (b)whoe gut transit time		9hours	No