- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03226145
Reclassifying Constipation Using Imaging and Manometry (RECLAIM)
Reclassifying Constipation Using Magnetic Resonance Imaging Combined With High Resolution Manometry: A Validation Study And Double-Blind Crossover Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
The study will involve both patients who suffer from constipation and also healthy volunteers.
There are two parts to the study. Participants with constipation will take part in both part 1 and part 2. Healthy volunteers will only take part in Part 1.
Part 1 of the study involves participants undergoing testing of their bowel function. It will involve 4 visits to the research centre. This is a validation study to compare MRI and HRM in their assessment of colonic motility. This will test 3 hypotheses: 1) MRI parameters of colonic physiology will correlate with HRM, 2) people with constipation who report greater abdominal pain and bloating will demonstrate greater colonic motility and frequency of retrograde contractions than those who report less bloating and abdominal pain, 3) MRI motility in the right colon will correlate with motility in the left colon.
Recruitment will be from hospital clinics as well as from the community by general advertisement. All assessments will be performed in NHS hospitals or Higher Education Institutions.
Once identified, potential participants will be sent an information sheet outlining their involvement. If they are happy to proceed they will be invited to attend the research unit (either Nottingham or London). On the first visit participants will be given all information required to give informed consent to take part. They will then be asked to complete questionnaires and a bowel diary to screen them. This will be for a 2 week period. The investigators will also access medical records in this time to help our assessment. They will return after this period and their diary/questionnaire will be assessed to ensure presence (constipation group) or absence (healthy control group) of bowel disorder. They will also be asked to have a blood test to ensure they have adequate renal function (necessary for the interventions) if they do not have one recorded in the last 3 months. They will also be asked to provide stool samples in this period.
If they meet the eligibility criteria following this they will be enrolled in the study.
Participants in the constipation group will then undergo a test for evacuation disorder called the balloon expulsion test. This is used in clinical practice to assess the function of the muscles used for defecation and it is thought to play a significant role in constipation overall. It involves inserting a thin catheter with a balloon which is filled with 50ml water. This provokes the feeling of needing to defecate and the patient will be asked to attempt to expel the balloon. They will be provided with a private toilet to do this and will be asked to time how long it takes. This measure will be recorded.
All participants (constipation group & healthy controls) will then undergo two tests. These are MRI and high resolution manometry. These will happen in a randomised order and will take place at least 1 week apart.
The MRI test day will be approximately 4 hours and will involve 3 sets of MRI images (each 30mins in length) and ingestion of a laxative drink to stimulate bowel movement which will then be analysed.
The Manometry recording day takes approximately 7 hours and involves an endoscopic procedure to place the manometry catheter in the bowel. Samples will also be taken from the bowel wall during this procedure. Once the catheter is placed the participant will remain in the research unit, be given a meal to consume and motility will be recorded for 4 hours (2hrs before meal and 2hrs after). They will undergo a single abdominal x-ray to record the position of the catheter in the bowel and it will be removed at the end of the day.
Following the completion of part 1, participants with constipation will proceed to part 2.
Part 2 looks at two currently used treatments - a prokinetic (bisacodyl) and a smooth muscle relaxant (buscopan).
There are 2 hypotheses that this will test: 1) (a) constipated patients with increased motility and/or increased contractions will respond better to a smooth muscle relaxant than to a stimulant prokinetic; (b) patients with hypomotility will respond better to a prokinetic, 2) There will be no difference between the performance of MRI and HRM as a predictor of clinical response.
The investigators will provide 2 capsules: A and B. One of the capsules will contain either Buscopan or Bisacodyl and the other an inert drug, the placebo. Whichever capsule is the placebo in the first 10 days trial will be replaced by the active drug in the second part. The order in which they are taken will be randomised so neither participant nor the research workers will know which active drug they are taking for each trial period.
This part of the study will involve 4 visits. At the first visit of these, the participant will be given the pills and instructions to take them. They will be asked to complete a daily symptom and bowel habit diary during the 10-day period and return these together with any unused pills at the second visit. After 2 weeks, they will be given the next set of capsules and again complete the daily diaries that they will return together with any unused pills at the end of the fourth visit . They will also be asked to complete one further questionnaire at the end of each treatment period. This will conclude the study.
A total of 120 participants (40 healthy, 40 FC, 40 IBS-C) will take part in the study and we estimate 4-6 weeks of time for the healthy volunteers and 12 weeks for the patient group.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Robin Spiller
- Phone Number: 31090 0115 951 5151
- Email: robin.spiller@nottingham.ac.uk
Study Contact Backup
- Name: Victoria Wilkinson-Smith
- Email: mszvw@exmail.nottingham.ac.uk
Study Locations
-
-
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London, United Kingdom
- Recruiting
- University College London
-
Contact:
- Laura Brockway
- Email: l.brockway@qmul.ac.uk
-
Contact:
- Stuart Taylor
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Principal Investigator:
- Stuart Taylor
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Sub-Investigator:
- David Atkinson
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Sub-Investigator:
- Anton Emmanuel
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London, United Kingdom
- Recruiting
- Queen Mary University of London
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Contact:
- Mark Scott
- Email: m.scott@qmul.ac.uk
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Contact:
- Laura Brockway
- Email: l.brockway@qmul.ac.uk
-
Principal Investigator:
- Mark Scott
-
Sub-Investigator:
- Charles Knowles
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Sub-Investigator:
- Henriette Heinrich
-
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Notts
-
Nottingham, Notts, United Kingdom, NG7 2RD
- Recruiting
- University of Nottingham
-
Contact:
- Victoria Wilkinson-Smith
- Phone Number: 7870554040
- Email: mszvw@exmail.nottingham.ac.uk
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Principal Investigator:
- Robin Spiller
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Sub-Investigator:
- Giles Major
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Sub-Investigator:
- Victoria Wilkinson-Smith
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Sub-Investigator:
- Maura Corsetti
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Sub-Investigator:
- Luca Marciani
-
Sub-Investigator:
- Caroline Hoad
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Sub-Investigator:
- Penny Gowland
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Aged ≥ 16 years
- Capacity to give informed consent for participation
- Ability to understand written and spoken English
- For Constipation Group: Symptoms of constipation meeting Rome IV criteria for functional constipation or constipation-predominant irritable bowel syndrome
- For Control Group: No symptoms of constipation. This will be defined as a score of 5 or less on the Cleveland Clinic Score
Exclusion Criteria:
1. Participation in any clinical trials in the past 3 months 2. Inability to understand written and spoken English 2.3. Pregnancy, assessed by a urinary pregnancy test, or current breastfeeding 3.4. History of significant adverse reaction or hypersensitivity, or known contra-indication to any of the medicinal products or equipment used in the study 4.5. History declared by the candidate of certain pre-existing gastrointestinal disorders, including:
- inflammatory bowel disease
- coeliac disease
- cancer of the gastrointestinal tract 5.6. Any reported history of gastrointestinal resection (excluding appendicectomy or cholecystectomy) 6.7. Presence of an intestinal stoma 7.8. Causes of secondary constipation disorders (e.g. systemic sclerosis / Parkinson's disease) 9. Inability to cease use of medicines that cause constipation or alter colonic contractility (e.g. opioids, smooth muscle relaxants, tricyclic antidepressants) 8.10. Antibiotic use in the last 3 months 9.11. Comorbidity that would prevent safe adherence to the protocol (e.g. inability to lie flat, kidney disease contraindicating use of Moviprep or prucalopride) 10.12. Judgement by the PI that the candidate who will be unable to comply with the full study protocol (e.g. diabetes, severe COPD) 11.13. Contraindication to MRI or colonic manometry
- Examples for MRI include claustrophobia, metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
- Examples for manometry include diagnosis of previous complications of diverticular disease or previous endoscopic complications 12.14. Clinical evidence of significant pelvic organ prolapse syndromes 13.15. Inadequate screening diary following review iii. Control Group: A screening diary that records <6 complete spontaneous bowel motions in the fortnight.
iv. Constipation Group: A screening diary that records <2 or >6 complete spontaneous bowel motions in the fortnight
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Patients
80 Patients : 40 FC 40 IBS-C Will have MRI Motility and High Resolution Manometry Then will have: Bisacodyl 10mg once daily for 10 days, and matched placebo hyoscine butylbromide Buscopan 20mg three times daily for 10 days, and matched placebo Both agents will have their matched placebo dispensed alongside the active product of the other agent. All agents to be used in this study as tools for their known mechanisms of action, rather than to assess their effects. |
MRI sequence to assess colonic motility
HRM of colon to assess motility
Given as agent to monitor effect on symptoms and then to compare with motility data.
Drug itself not being tested.
Given as agent to monitor effect on symptoms and then to compare with motility data.
Drug itself not being tested.
Other Names:
|
ACTIVE_COMPARATOR: Healthy Volunteers
40 HVs Will have MRI Motility and High Resolution Manometry No other interventions
|
MRI sequence to assess colonic motility
HRM of colon to assess motility
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MRI Endpoint: Maximal MRI Motility Index (MMI) of the ascending colon (AC)
Time Frame: During MRI scan (over 3 hours)
|
MRI Measure of Colonic Motility
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During MRI scan (over 3 hours)
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HRM Endpoint: Percentage time occupied by cyclical propagating activity following meal
Time Frame: During manometry recording (over 6 hours)
|
Manometry recording of colonic motility
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During manometry recording (over 6 hours)
|
Difference in average worst daily pain, scored on a range 1-5 between buscopan and bisacodyl intervention periods.
Time Frame: Over 10 day period
|
Over 10 day period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximal MMI of the descending colon (DC)
Time Frame: During MRI scan (over 3 hours)
|
During MRI scan (over 3 hours)
|
|
Whole Gut Transit
Time Frame: Weighted Average Position Score of MRI transit markers 24 hours after ingestion
|
Weighted Average Position Score of MRI transit markers 24 hours after ingestion
|
|
Number of complete spontaneous bowel movements.
Time Frame: 10 day period whilst on intervention (prucalopride/buscopan)
|
CSBM is defined as a bowel movement occurring more than 24 hours after the most recent dose of rescue therapy, where the participant perceives complete evacuation of their rectum.
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10 day period whilst on intervention (prucalopride/buscopan)
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Stool consistency
Time Frame: 10 day period whilst on intervention (bisacodyl/buscopan)
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Defined as days per week of type 1& 2 on the Bristol Stool Form Scale (that has an integer range from 1-7)
|
10 day period whilst on intervention (bisacodyl/buscopan)
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PAC-SYM Questionnaire Score
Time Frame: Throughout study. Baseline then at end of each 10 day intervention period.
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Throughout study. Baseline then at end of each 10 day intervention period.
|
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Area Under the Curve for pressure 0-30 minute during HRM Number of High Amplitude Propagating Contractions (HAPCs)
Time Frame: During manometry recording ( 6 hours)
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During manometry recording ( 6 hours)
|
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Number of High Amplitude Propagating Contractions (HAPCs) during HRM
Time Frame: During manometry recording ( 6 hours)
|
During manometry recording ( 6 hours)
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Signs and Symptoms, Digestive
- Gastrointestinal Diseases
- Colonic Diseases, Functional
- Colonic Diseases
- Intestinal Diseases
- Irritable Bowel Syndrome
- Constipation
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Parasympatholytics
- Autonomic Agents
- Peripheral Nervous System Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Antiemetics
- Gastrointestinal Agents
- Adjuvants, Anesthesia
- Cathartics
- Laxatives
- Mydriatics
- Bisacodyl
- Scopolamine
- Butylscopolammonium Bromide
Other Study ID Numbers
- 16105
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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