Reclassifying Constipation Using Imaging and Manometry

NCT03226145 | Unknown

• 1 other identifier: 16105
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

Constipation is a common condition in which an individual suffers with hard stools which are infrequent and difficult to pass. It is poorly understood and treatment is often unsatisfactory. Many patients also experience pain whilst others do not but it is unclear why . It is believed that the pain arises from contractions in the colon, the lower part of the intestines. Some patients with constipation have weak colonic contraction but surprisingly some, particularly those with a lot of pain have strong contractions which are poorly coordinated. These patients all suffer from constipation but would are likely to need very different treatments. At present we cannot identify what type of abnormality of colonic contractions each individual patient suffers from and so are unable to give them the best treatment. This study will take advantage of two new techniques which have been recently developed. Magnetic Resonance Imaging (MRI) which will allow us to see the contractions of the colon in response to a dose of the laxative Moviprep which increases the flow of fluid into the proximal part of the colon and High Resolution Manometry (HRM) which measures the power and direction of the contraction in much more detail than ever before using a pressure sensing catheter placed into the bowel. Using these 2 techniques we will identify the pattern of contractions in 80 patients with constipation and 40 healthy controls. Participants will then enter into a controlled trial of either a drug which stimulates contractions or one which inhibits contraction. We anticipate that the pattern of contractions identified by the non-invasive MRI technique will predict which treatment will reduce their symptoms most as effectively as the more invasive HRM. If this is the case then our MRI test of colonic responsiveness could become widely used in routine clinical practice

Conditions

Constipation - Functional; Irritable Bowel Syndrome Characterized by Constipation

Outcome Measures

Primary Outcomes (3)

• MRI Endpoint: Maximal MRI Motility Index (MMI) of the ascending colon (AC)

  MRI Measure of Colonic Motility

  During MRI scan (over 3 hours)

• HRM Endpoint: Percentage time occupied by cyclical propagating activity following meal

  Manometry recording of colonic motility

  During manometry recording (over 6 hours)

• Difference in average worst daily pain, scored on a range 1-5 between buscopan and bisacodyl intervention periods.

  Over 10 day period

Secondary Outcomes (7)

• Maximal MMI of the descending colon (DC)

  During MRI scan (over 3 hours)

• Whole Gut Transit

  Weighted Average Position Score of MRI transit markers 24 hours after ingestion

• Number of complete spontaneous bowel movements.

  10 day period whilst on intervention (prucalopride/buscopan)

• Stool consistency

  10 day period whilst on intervention (bisacodyl/buscopan)

• PAC-SYM Questionnaire Score

  Throughout study. Baseline then at end of each 10 day intervention period.

Study Arms (2)

Patients

ACTIVE COMPARATOR

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.

Procedure: MRI Motility; Procedure: High Resolution Manometry; Drug: Bisacodyl; Drug: Hyoscine butylbromide

Healthy Volunteers

ACTIVE COMPARATOR

40 HVs Will have MRI Motility and High Resolution Manometry No other interventions

Procedure: MRI Motility; Procedure: High Resolution Manometry

Interventions

MRI Motility PROCEDURE

MRI sequence to assess colonic motility

Healthy Volunteers; Patients

High Resolution Manometry PROCEDURE

HRM of colon to assess motility

Healthy Volunteers; Patients

Bisacodyl DRUG

Given as agent to monitor effect on symptoms and then to compare with motility data. Drug itself not being tested.

Patients

Hyoscine butylbromide DRUG

Given as agent to monitor effect on symptoms and then to compare with motility data. Drug itself not being tested.

Also known as: Buscopan

Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \. 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

Sponsors & Collaborators

• University of Nottingham: lead
• University College, London: collaborator
• Queen Mary University of London: collaborator

Study Sites (3)

University of Nottingham

Nottingham, Notts, NG7 2RD, United Kingdom

RECRUITING

Queen Mary University of London

London, United Kingdom

RECRUITING

University College London

London, United Kingdom

RECRUITING

Related Publications (1)

• Wilkinson-Smith V, Scott M, Menys A, Wiklendt L, Marciani L, Atkinson D, Sansone S, Zdanaviciene A, Coupland C, Knowles CH, Dinning P, Taylor SA, Gowland P, Hoad CL, Corsetti M, Spiller RC. Combined MRI, high-resolution manometry and a randomised trial of bisacodyl versus hyoscine show the significance of an enlarged colon in constipation: the RECLAIM study. Gut. 2024 Dec 10;74(1):35-44. doi: 10.1136/gutjnl-2024-332755.

  PMID: 39438126 DERIVED

MeSH Terms

Interventions

Bisacodyl; Butylscopolammonium Bromide

Intervention Hierarchy (Ancestors)

Cresols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quaternary Ammonium Compounds; Amines; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Robin Spiller

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robin Spiller

CONTACT

0115 951 5151; robin.spiller@nottingham.ac.uk

Victoria Wilkinson-Smith

CONTACT

mszvw@exmail.nottingham.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: July 21, 2017
• Study Start: July 20, 2017
• Primary Completion: September 1, 2020
• Study Completion: June 1, 2021
• Last Updated: July 7, 2020

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)