MRI and Microbiota Analysis in Constipation

Constipation Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02144376
• Other study ID #: UON14011
• Secondary ID: 14GA006
• Status: Completed
• Phase: N/A
• First received: March 25, 2014
• Last updated: January 4, 2017
• Start date: March 2014
• Est. completion date: June 2016

Study information

• Verified date: January 2017
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: National Institute for Health Research
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2016
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Constipation

Intervention

Dietary Supplement:
• Ispaghula

• Maltodextrin

Locations

Country	Name	City	State
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	University of Nottingham	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
University of Nottingham	Ironwood Pharmaceuticals, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Colonic volume	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)	-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal	No
Other	Colonic gas volume	Area under the curve (mL.min), measured on hourly MRI scans by segmentation into AC, TC and DC	-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal	No
Other	Gastric volume	Area under the curve (mL.min) measured on hourly MRI scans	-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal	No
Other	Abdominal circumference	Measured at the umbilicus in cm, determined by MRI	-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal	No
Other	Change from baseline of stool water content percentage by mass	Stool will be sampled during the baseline week and between days 3-7 of the intervention week during each treatment period	after an average 5 days of intervention	No
Other	Change from baseline in stool frequency	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.	during days 9-14 of treatment period	No
Other	Change from baseline in stool consistency	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.	During days 9-14 of treatment period	No
Other	Change from baseline in faecal microbiota	Will be assessed for relative abundance, richness and diversity	Change from baseline after an average 5 days of intervention	No
Other	Change from baseline in faecal short-chain fatty acids	Stool samples collected during baseline week and after 3 or more days of intervention in each treatment period.	Change from baseline after an average 5 days of intervention	No
Other	Symptoms during study day	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	-60, 0, 60, 120, 180, 240, 300, 360, 420 minutes after test meal	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No