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MRI and Microbiota Analysis in Constipation (MIMIC)

Primary Purpose

Constipation

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Ispaghula
Maltodextrin
Sponsored by
University of Nottingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Constipation focused on measuring Constipation, psyllium, ispaghula, Magnetic Resonance Imaging, MRI, microbiota

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Nottingham University Hospitals NHS Trust
  • University of Nottingham

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Maltodextrin

Ispaghula

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Small Bowel Water Content (SBWC) in millilitres(mL) measured by MRI
Area under the curve (mL.min) will be calculated from hourly MRI scans
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.
Ascending Colon Water Content in millilitres measured by MRI
After 5 days taking study product participants will undergo an MRI scan while fasted
Ascending Colon Water Content in millilitres measured by MRI
Area under the curve (mL.min) will be calculated from hourly MRI scans
Change from baseline in Ascending Colon Water Content in millilitre measured by MRI
Difference between measurement Meal -60 (fasting) and 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
Ascending Colon T1
Area under the curve of MRI parameter measured at hourly time points
Descending Colon T1
Area under the curve of MRI parameter measured at hourly time points
Ascending colon T2
Area under the curve of MRI parameter measured at hourly time points
Descending Colon T2
Area under the curve of MRI parameter measured at hourly time points

Full Information

First Posted
March 25, 2014
Last Updated
January 4, 2017
Sponsor
University of Nottingham
Collaborators
Ironwood Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02144376
Brief Title
MRI and Microbiota Analysis in Constipation
Acronym
MIMIC
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

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nottingham
Collaborators
Ironwood Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Constipation
Keywords
Constipation, psyllium, ispaghula, Magnetic Resonance Imaging, MRI, microbiota

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Maltodextrin
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Ispaghula
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Dietary Supplement
Intervention Name(s)
Ispaghula
Other Intervention Name(s)
psyllium
Intervention Type
Dietary Supplement
Intervention Name(s)
Maltodextrin
Primary Outcome Measure Information:
Title
Weighted Average Position Score of transit marker capsules as determined by MRI
Description
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
Time Frame
24 hours after ingestion
Secondary Outcome Measure Information:
Title
Weighted Average Position Score of 5 transit marker capsules, as determined by MRI
Description
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
Time Frame
48 hours after ingestion
Title
Small Bowel Water Content (SBWC) in millilitres(mL) measured by MRI
Description
Area under the curve (mL.min) will be calculated from hourly MRI scans
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Small Bowel Water Content (SBWC) in millilitres measured by MRI
Description
After 5 days of taking the study product participants will undergo an MRI scan while fasted.
Time Frame
Baseline, 60 minutes before test meal
Title
Ascending Colon Water Content in millilitres measured by MRI
Description
After 5 days taking study product participants will undergo an MRI scan while fasted
Time Frame
Baseline, 60 minutes before test meal
Title
Ascending Colon Water Content in millilitres measured by MRI
Description
Area under the curve (mL.min) will be calculated from hourly MRI scans
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Change from baseline in Ascending Colon Water Content in millilitre measured by MRI
Description
Difference between measurement Meal -60 (fasting) and Meal +60
Time Frame
test meal -60, test meal +60
Title
Change from before to after challenge meal in Ascending Colon Water Content before in millilitre measured by MRI
Description
Difference between time points Meal2 -20 and Meal 2 +40
Time Frame
test meal +360 minutes, test meal + 420 minutes
Title
Ascending Colon T1
Description
Area under the curve of MRI parameter measured at hourly time points
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Descending Colon T1
Description
Area under the curve of MRI parameter measured at hourly time points
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Ascending colon T2
Description
Area under the curve of MRI parameter measured at hourly time points
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Descending Colon T2
Description
Area under the curve of MRI parameter measured at hourly time points
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Other Pre-specified Outcome Measures:
Title
Colonic volume
Description
Area under the curve (mL.min) will be measured from hourly MRI scans by segmentation into ascending colon (AC), transverse colon (TC) and descending colon (DC)
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Colonic gas volume
Description
Area under the curve (mL.min), measured on hourly MRI scans by segmentation into AC, TC and DC
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Gastric volume
Description
Area under the curve (mL.min) measured on hourly MRI scans
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Abdominal circumference
Description
Measured at the umbilicus in cm, determined by MRI
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal
Title
Change from baseline of stool water content percentage by mass
Description
Stool will be sampled during the baseline week and between days 3-7 of the intervention week during each treatment period
Time Frame
after an average 5 days of intervention
Title
Change from baseline in stool frequency
Description
Each treatment period includes 1 day washout, 7 days baseline, up to 7 (minimum 6) days intervention. Total = 15 days. Stool frequency will be sampled on days 2-8 and 9-14, since participants may stop taking intervention before day 15.
Time Frame
during days 9-14 of treatment period
Title
Change from baseline in stool consistency
Description
Each treatment period includes 1 day washout, 7 days baseline, up to 7 (minimum 6) days intervention. Total = 15 days. Stool consistency will be sampled on days 2-8 and 9-14, since participants may stop taking intervention before day 15.
Time Frame
During days 9-14 of treatment period
Title
Change from baseline in faecal microbiota
Description
Will be assessed for relative abundance, richness and diversity
Time Frame
Change from baseline after an average 5 days of intervention
Title
Change from baseline in faecal short-chain fatty acids
Description
Stool samples collected during baseline week and after 3 or more days of intervention in each treatment period.
Time Frame
Change from baseline after an average 5 days of intervention
Title
Symptoms during study day
Description
4 symptoms will be measured on 2 scales: a previously validated questionnaire on an ordinal scale (OS) of 0 (none), 1 (mild/ distinct but negligible), 2 (moderate/ annoying), 3 (severe/ disabling); and a Visual Analogue Scale (VAS) (0-100) Symptoms include abdominal pain, bloating, gas/flatulence, and diarrhoea. Clinically important symptoms will be defined as additive total score of 3 or greater on OS. VAS scores will be analysed alongside MRI data
Time Frame
-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robin Spiller, MSc MD FRCP
Organizational Affiliation
University of Nottingham
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Giles Major, BM BCh MRCP
Organizational Affiliation
University of Nottingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Luca Marciani, MSc PhD
Organizational Affiliation
University of Nottingham
Official's Role
Study Director
Facility Information:
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Facility Name
University of Nottingham
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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MRI and Microbiota Analysis in Constipation

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