Clinical trial NCT02144376: MRI and Microbiota Analysis in Constipation
Official title: Validation of Magnetic Resonance Imaging to Characterise Gastrointestinal Physiology, Gut Luminal Content and Its Interaction With Colonic Microbiota in Patients With Chronic Constipation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Constipation
Keywords: Constipation
psyllium
ispaghula
Magnetic Resonance Imaging
MRI
microbiota
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2014-05-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to test how well magnetic resonance imaging (MRI) can measure whole gut transit time in people with constipation, and how readily it can detect a change in transit time induced by taking a dietary supplement with laxative effects.The investigators expect to demonstrate that ispaghula (psyllium) accelerates movement of matter through the intestinal tract.

The investigators will also assess whether a change in gut bacteria and the chemicals that they release can be detected.


Eligibility criteria: Inclusion Criteria:

* Meets Rome III Criteria for diagnosis of Functional Constipation5 on questionnaire (NB. Both those who do and do not meet IBS criteria will be eligible)
* At least one bowel motion per week while taking usual laxatives
* Able to give informed consent
* Aged 18 or older

Exclusion Criteria:

* History declared by the candidate of other pre-existing gastrointestinal disorder, including but not limited to:
* Inflammatory Bowel Disease
* Coeliac Disease diagnosed in the last year
* Pancreatitis
* Cancer of the gastrointestinal tract
* Any reported history of gastrointestinal resection (excluding appendicectomy or cholecystectomy)
* Presence of an intestinal stoma
* Pregnancy declared by candidate (no formal testing)
* Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
* Reported alcohol intake of \>28 units/ week with daily drinking
* Any use of a product containing ispaghula or psyllium in the 4 weeks prior to consent
* Unable to avoid use of dihydrocodeine or morphine during the study
* If taking other regular opiates such as codeine, fentanyl or Oxycodone, participants should be able to maintain a stable dose throughout the study
* Any reported history of hypersensitivity or significant adverse reaction to ispaghula, maltodextrin or bisacodyl
* Unable to stop drugs and other agents used primarily for their laxative effect, during periods of screening, washout, baseline and treatment (maximum 15 days - rescue medication will be provided).
* Antibiotic or prescribed probiotic treatment in the past 4 weeks
* Inability to lie flat or exceed scanner limits of weight \<120kg
* Poor understanding of English language
* Participation in any medical trials for the past 3 months
* Any condition where the candidate is likely to require a course of antibiotics in the next 3 months e.g. severe chronic respiratory disease, recurrent urinary tract infection, lower limb ulceration
* Judgement by the PI that the candidate who will be unable to comply with the full study protocol e.g. Diabetes, severe COPD

During the screening 2 weeks off laxatives

* No bowel motions recorded during screening period
* ≥3 complete spontaneous bowel motions (CSBMs - bowel motion with the feeling of complete evacuation, without the use of rescue therapy in the preceding 24 hours) per week

Primary outcomes:
measure: Weighted Average Position Score of transit marker capsules as determined by MRI
timeFrame: 24 hours after ingestion
Secondary outcomes:
measure: Weighted Average Position Score of 5 transit marker capsules, as determined by MRI
timeFrame: 48 hours after ingestion
measure: Small Bowel Water Content (SBWC) in millilitres(mL) measured by MRI
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Small Bowel Water Content (SBWC) in millilitres measured by MRI
timeFrame: Baseline, 60 minutes before test meal
measure: Ascending Colon Water Content in millilitres measured by MRI
timeFrame: Baseline, 60 minutes before test meal
measure: Ascending Colon Water Content in millilitres measured by MRI
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Change from baseline in Ascending Colon Water Content in millilitre measured by MRI
timeFrame: test meal -60, test meal +60
measure: Change from before to after challenge meal in Ascending Colon Water Content before in millilitre measured by MRI
timeFrame: test meal +360 minutes, test meal + 420 minutes
measure: Ascending Colon T1
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Descending Colon T1
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Ascending colon T2
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Descending Colon T2
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Other outcomes:
measure: Colonic volume
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Colonic gas volume
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Gastric volume
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Abdominal circumference
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
measure: Change from baseline of stool water content percentage by mass
timeFrame: after an average 5 days of intervention
measure: Change from baseline in stool frequency
timeFrame: during days 9-14 of treatment period
measure: Change from baseline in stool consistency
timeFrame: During days 9-14 of treatment period
measure: Change from baseline in faecal microbiota
timeFrame: Change from baseline after an average 5 days of intervention
measure: Change from baseline in faecal short-chain fatty acids
timeFrame: Change from baseline after an average 5 days of intervention
measure: Symptoms during study day
timeFrame: -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Nottingham
country: United Kingdom
facility: University of Nottingham
Study officials:
affiliation: University of Nottingham
name: Robin Spiller, MSc MD FRCP
role: STUDY_CHAIR
affiliation: University of Nottingham
name: Giles Major, BM BCh MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Luca Marciani, MSc PhD
role: STUDY_DIRECTOR
References: