MRI and Microbiota Analysis in Constipation

Study Overview
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Brief Summary
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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.

Official Title
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Validation of Magnetic Resonance Imaging to Characterise Gastrointestinal Physiology, Gut Luminal Content and Its Interaction With Colonic Microbiota in Patients With Chronic Constipation

Conditions
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Constipation

Intervention / Treatment
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* Dietary Supplement: Ispaghula
* Dietary Supplement: Maltodextrin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Maltodextrin<br>7 days without use of laxatives other than standardised rescue therapy 7 grams maltodextrin taken 3 times daily, at least 4 hours apart, for up to 7 days | Dietary Supplement: Maltodextrin<br> <br> |
| Active Comparator: Ispaghula<br>7 days without use of laxatives other than standardised rescue therapy 7 grams ispaghula/ psyllium taken 3 times daily, at least 4 hours apart, for up to 7 days | Dietary Supplement: Ispaghula<br> <br> * Other names: psyllium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Average Position Score of transit marker capsules as determined by MRI | After 4 days of study product participants will ingest 5 transit mark capsules, the use of which has been shown to measure whole gut transit in a similar manner to more established techniques. They will continue to take study product before undergoing an MRI scan to assess capsule position | 24 hours after ingestion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Average Position Score of 5 transit marker capsules, as determined by MRI | After 4 days of study product participants will ingest 5 transit mark capsules, the use of which has been shown to measure whole gut transit in a similar manner to more established techniques. They will continue to take study product before undergoing an MRI scan to assess capsule position | 48 hours after ingestion | 
| Small Bowel Water Content (SBWC) in millilitres(mL) measured by MRI | Area under the curve (mL.min) will be calculated from hourly MRI scans | -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal | 
| Small Bowel Water Content (SBWC) in millilitres measured by MRI | After 5 days of taking the study product participants will undergo an MRI scan while fasted. | Baseline, 60 minutes before test meal | 
| Ascending Colon Water Content in millilitres measured by MRI | After 5 days taking study product participants will undergo an MRI scan while fasted | Baseline, 60 minutes before test meal | 
| Ascending Colon Water Content in millilitres measured by MRI | Area under the curve (mL.min) will be calculated from hourly MRI scans | -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal | 
| Change from baseline in Ascending Colon Water Content in millilitre measured by MRI | Difference between measurement Meal -60 (fasting) and Meal +60 | test meal -60, test meal +60 | 
| Change from before to after challenge meal in Ascending Colon Water Content before in millilitre measured by MRI | Difference between time points Meal2 -20 and Meal 2 +40 | test meal +360 minutes, test meal + 420 minutes | 
| Ascending Colon T1 | Area under the curve of MRI parameter measured at hourly time points | -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal | 
| Descending Colon T1 | Area under the curve of MRI parameter measured at hourly time points | -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal | 
| Ascending colon T2 | Area under the curve of MRI parameter measured at hourly time points | -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal | 
| Descending Colon T2 | Area under the curve of MRI parameter measured at hourly time points | -60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Constipation, psyllium, ispaghula, Magnetic Resonance Imaging, MRI, microbiota