Immune responses to stool of patients with inflammatory bowel diseases treated with anti-TNF therapies
| ISRCTN | ISRCTN62674004 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN62674004 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 264405 |
| Protocol serial number | IRAS 264405 |
| Sponsor | West Hertfordshire Hospitals NHS Trust |
| Funder | Investigator initiated and funded |
- Submission date
- 09/03/2022
- Registration date
- 18/03/2022
- Last edited
- 18/03/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Inflammatory bowel disease (IBD) is a term mainly used to describe 2 conditions: ulcerative colitis and Crohn's disease. Ulcerative colitis and Crohn's disease are long-term conditions that involve inflammation of the gut. Ulcerative colitis only affects the colon (large intestine). Crohn's disease can affect any part of the digestive system, from the mouth to the bottom (anus).
Anti-TNF therapies (TNF inhibitors are drugs that help stop inflammation) remain the mainstay biologic treatment for inflammatory bowel disease (IBD) patients. These are hugely costly and the efficacy of any one of these agents are still limited with side-effects that can be potentially severe and life-threatening. Between 20–40% of patients do not respond to anti-TNF therapies and a further 25% of patients lose response over the first year of treatment. Predictors of efficacy for anti-TNF treatment would be extremely useful in clinical practice in order to optimise treatments and to minimise side-effects and costs. There is an urgent need to personalise therapeutic choices to avoid unnecessary delays in treatment benefit, avoidance of adverse effects and to reduce costs.
Recent data suggest that the microbiota may offer a non-invasive predictive tool to predict response to anti-TNF therapy as well as response to other biologic therapies. Macrophage (immune cell) expression of inflammatory regulators that respond to microbial signalling were also recently identified as potential predictors of anti-TNF therapy response and that an altered microbiome composition may influence expression of macrophage inflammatory regulator expression and subsequently anti-TNF responsiveness.
We aim to conduct this pilot study to assess differences of macrophage characteristics when co-cultured with faecal supernatants from anti-TNF responders and non-responders with Crohn's disease and Ulcerative colitis.
Who can participate?
Inflammatory bowel disease patients initiating anti-TNF therapy
What does the study involve?
Blood samples, stool samples, and biopsies will be taken in addition for research purposes where patients are undergoing interventions as part of routine clinical care.
What are the possible benefits and risks of participating?
None
Where is the study run from?
West Hertfordshire Teaching Hospitals NHS Trust (UK)
When is the study starting and how long is it expected to run for?
October 2021 to July 2024
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Dr Jonathan Landy, jonathan.landy@nhs.net
Contact information
Principal investigator
Gastroenterology department
Watford Hopsital
Vicarage Road
Watford
WD18 0HB
United Kingdom
 ORCID ID |
0000-0003-1201-3346 |
|---|---|
| Phone | +44 1442287682 |
| jonathan.landy@nhs.net |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Single centre longitudinal observational cohort study |
| Secondary study design | Cohort study |
| Study type | Participant information sheet |
| Scientific title | Study of monocyte/macrophage responses to faecal supernatants of anti-TNF responsive and non-responsive IBD patients. |
| Study objectives | Faecal supernatants from inflammatory bowel disease patients that are subsequently responsive to anti-TNF therapy will exert a distinct phenotype and function of monocytes/macrophages when co-cultured. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Inflammatory bowel disease |
| Intervention | Blood samples, stool samples, and biopsies will be taken in addition for research purposes where patients are undergoing interventions as part of routine clinical care. |
| Intervention type | Other |
| Primary outcome measure(s) |
Phenotype of monocyte/macrophages and monocyte/macrophage response to faecal supernatant measured using: |
| Key secondary outcome measure(s) |
Clinical evaluation of patients records and bloods including CRP, Albumin and haemoglobin and stool tests including faecal calprotectin will be taken at baseline and at weeks 14, 30 and 52 or at the point of loss of response after initiating anti-TNF therapy. |
| Completion date | 01/07/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 20 |
| Key inclusion criteria | Inflammatory bowel disease patients initiating anti-TNF therapy |
| Key exclusion criteria | 1. Crohn’s disease without ileal or colonic involvement 2. Ulcerative proctitis 3. Pregnancy |
| Date of first enrolment | 01/08/2022 |
| Date of final enrolment | 01/08/2023 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Vicarage Road
Watford
WD18 0HB
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available. Patient data will be stored on hospital computers and password protected at all times. All data will be link anonymised and held securely. No individuals will be identified in published data. De-identified data will be analysed by the research investigators. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version 2 | 29/12/2021 | 14/03/2022 | No | No |
Additional files
- 41326 Protocol v2 29Dec2021.pdf
- Protocol file
Editorial Notes
18/03/2022: Trial's existence confirmed by NHS HRA
