Investigating the effects of resolving intestinal narrowing in Crohn’s disease – a study of gut bacteria, movement and products

ISRCTN ISRCTN14328524
DOI https://doi.org/10.1186/ISRCTN14328524
IRAS number 252808
Secondary identifying numbers DHRD/2018/078, IRAS 252808
Submission date
26/12/2018
Registration date
20/02/2019
Last edited
18/07/2023
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Crohn’s disease (CD) is a chronic gastrointestinal condition with serious health implications. CD is characterised by the presence of small and large bowel inflammation. CD patients frequently experience abdominal pain, nausea, and diarrhoea. These symptoms may result from ‘narrowings’ within the bowel known as ‘strictures'. Crohn’s patients who have intestinal surgery experience ‘stricturing’ (the formation of strictures) more often.

The ‘CS3M Crohn’s Stricture Study’ will give new insights into ‘strictures’ in this context. There are many unanswered questions. It is unclear how strictures affect bowel contraction, bacteria within the gut and bacterial by-products. It is also not clear how to best treat patients with strictures.

This study will investigate four separate aspects of intestinal strictures in Crohn’s disease:
1. How stenting of strictures affects the movement of the bowel (a.k.a. motility).
2. How stenting of strictures affects the bacterial content of the gut (a.k.a. microbiome).
3. How stenting of the strictures affects bacterial by-products from the gut (a.k.a. metabolomics).
4. The clinical impact of CD stricture stenting.

The results from this pilot study may inform future large scale trials involving stenting in CD. This research will generate novel data about stenting impact in CD and will consist of the first global report such findings.

Who can participate?
Only Crohn’s disease patients with identified ‘intestinal strictures’ will be asked to participate. Several different treatment options exist. Intestinal ‘stenting’ is one of the available therapies. It involves the endoscopic placement of an opening device, known as a ‘stent’, into the affected area.
Should a patient choose to undergo stent therapy, they will then be asked to take part in the study. Only adult patients (ages 18-80), who can give consent and are not enrolled in other research studies will be eligible. No healthy controls will be enrolled in the study.

What does the study involve?
Each patient will undergo a Magnetic Resonance (MR) scan before and after stent treatment. Stool samples will be collected prior to and following ‘stenting’. These stool samples will be analysed for bacterial content and by-products. The techniques used for stool analysis will include bacterial genetic analysis and gas-chromatography analysis of bacterial metabolites. Each patient’s clinical progress will be reviewed and assessed with validated Inflammatory Bowel Disease (IBD) scoring tools.

What are the possible benefits and risks of participating?
The risks to each study participant (from stool collection, and MRI scanning) has been deemed to be low. The novel insights into strictures in CD will be delivered by data produced by stool analysis and MRI scans of the intestine. Clinical data will further our understanding of stent treatment in Crohn’s disease. Personal research findings will be relayed to study participants.

Where is the study run from?
All study activities will be conducted at a single research centre - Royal Derby Hospital – UK. The study is being sponsored by the University of Nottingham.

When is the study starting and how long is it expected to run for?
Beginning from January 2019, the study will run for a total of 18 months.

Who is funding the study?
All study activities are being funded by an internal Royal Derby Hospital - Gastroenterology research fund and a further Royal Derby Hospital charity source.

Who is the main contact?
Dr Ronit Das, ronitkdas@gmail.com

Study website

Contact information

Dr Ronit Das
Public

Room 4110 - University of Nottingham
Department of Health Sciences
Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom

ORCiD logoORCID ID 0000-0002-3539-8894
Phone +44 1332 340131
Email ronitkdas@gmail.com

Study information

Study designPilot observational cohort study
Primary study designObservational
Secondary study designCohort study
Study setting(s)Hospital
Study typeOther
Participant information sheet http://www.cs3m.online/
Scientific titleCharacterising the effects of relieving stricture obstruction by ileocolonic stenting - a pilot study into motility, microbiomics and metabolomics in Crohn’s disease
Study acronymCS3M
Study objectivesThe relief of ileocolonic, Crohn’s stricture-related mechanical obstruction has a quantifiable impact on bowel motility, the intestinal bacterial population and associated metabolomic profiles.
Ethics approval(s)Health and Social Care Research Ethics Committee B (HSC REC B), 24/12/2018, ref. 18/NI/0241
Health condition(s) or problem(s) studiedCrohn's Disease.
InterventionPatients with Crohn’s disease and abnormal intestinal ‘narrowings’ (known as ‘strictures’) will be asked to take part in the study. Each patient will have routine clinical treatment of their ‘stricture’ with a removable expanding device. Before and after treatment, specific studies will be performed. Each patient with undergo two intestinal MRI scans examining gut movements. Stool samples will be collected before and following therapy. Each stool sample will be analysed for bacterial content and separate chemical by-products. Patient progress will be monitored throughout the study. The total time of involvement for each patient will be between 8 to 10 months.
Intervention typeOther
Primary outcome measure1. The bowel microbiome will be measured using stool bascterial 16sRNA analysis pre-therapy, during therapy and post-therapy.
2. Intestinal motility will be measured using magnetic resonance-assessed small bowel motility at baseline and after 6 weeks of therapy.
3. The stool metabolic profile will be measured using gas-chromatography stool metabolomic analysis pre-therapy and post-therapy.
4. Clinical impact on Crohn’s ileocolonic strictures will be measured using paired assessment with validated IBD scoring tools (CDAI, HBI, IBD-Q) at baseline and at 6-8 weeks.
Secondary outcome measures1. Progression onto Surgery
2. Recruitment Rate
3. Complications / Adverse Events
Overall study start date01/05/2018
Completion date01/01/2021

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants14
Key inclusion criteria1. Crohn’s Disease as an established diagnosis (established diagnosis based on histology and supportive imaging)
2. Previous right hemicolectomy or partial resection and subsequent large and small bowel re-anastomosis
3. Identified anastomotic or de novo stricture accessible by colonoscopy – endoscopic or imaging identification (MR or CT or endoscopy)
4. Aged 16-80 years
5. Symptoms attributable to a focal ileocolonic stricture
6. Ability to give informed consent
Inclusion into the study will only be following Inflammatory Bowel Disease Multidisciplinary Team referral and strict adherence to the given inclusion criteria.
Key exclusion criteria1. Malignancy
2. Significant cardiovascular or respiratory disease
3. Uncontrolled thyroid disease
4. Neurological or cognitive impairment
5. Significant physical disability
6. Hepatic disease or renal failure
7. Abnormal blood results other than those explained by CD in CD participants
8. Co-enrolment in other CD study
9. Pregnancy or ongoing breastfeeding
10. Any condition that precludes MRI scanning (e.g. pacemaker)
11. Routine usage of any medication that affects gastric emptying or small bowel motility (i.e. hyoscine butylbromide, mebeverine, domperidone, ondansetron, metoclopramide)
12. Inability to endoscopically access stricture or place stent
Date of first enrolment10/04/2019
Date of final enrolment01/03/2020

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Sponsor information

University of Nottingham
University/education

Research and Innovation.
East Atrium
Jubilee Conference Centre
Triumph Road
Nottingham
NG8 1DH
England
United Kingdom

Phone 0115 8467103
Email sponsor@nottingham.ac.uk
Website https://www.nottingham.ac.uk/
ROR logo "ROR" https://ror.org/01ee9ar58

Funders

Funder type

Hospital/treatment centre

Gastroenterology Departmental Research Fund - Royal Derby Hospital

No information available

Charitable Fund - Royal Derby Hospital

No information available

Results and Publications

Intention to publish date01/12/2022
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination planPublication of results is expected in peer-reviewed journals within 12 months of trial end.
IPD sharing planThe datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No

Editorial Notes

18/07/2023: The contact email was updated.
23/03/2022: The intention to publish date has been changed from 01/12/2021 to 01/12/2022.
30/10/2020: The overall trial end date has been changed from 01/09/2020 to 01/01/2021.
06/09/2019: The recruitment start date was changed from 30/01/2019 to 10/04/2019.