Faecal microbiota transplantation in ulcerative colitis

ISRCTN ISRCTN58082603
DOI https://doi.org/10.1186/ISRCTN58082603
Secondary identifying numbers N/A
Submission date
02/07/2015
Registration date
24/07/2015
Last edited
09/04/2019
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
Ulcerative colitis (UC) is a chronic, relapsing debilitating form of inflammatory bowel disease. The number of people suffering from the condition in the UK is increasing. The cause is unknown but is considered to result from the body’s response to bacteria found in the large intestine in genetically susceptible individuals. Current treatment aims to dampen the immune response with daily tablets and enemas, although symptoms often return once medication is stopped. On occasion, medical treatment doesn’t work and surgery to remove the large intestine is required. It has been suggested that if the bacteria present in the large intestine in UC patients were replaced with those found in healthy people then the immune damage would reverse. Administration of healthy bacteria to repopulate the bowel (faecal bacteriotherapy, FBT) is a recommended treatment for certain bowel infections, such as Clostridium difficile colitis, and the therapy has been shown to be safe and work well. The first report of FBT as a treatment for UC was in 1989, with reports of patients remaining in remission for up to 25 years. Studies are however limited to small patient series with variable methodology, including route of administration and dose frequency, and a lack of standardisation. This study aims to find out the optimal conditions in which to conduct a large scale study of FBT in patients with limited UC. We want to know the optimal frequency of FMT administration by the enema route (single dose or 5 doses) in patients with inflammation limited to the rectum and sigmoid colon compared with a control group.

Who can participate?
Patients aged at least 18 with UC.

What does the study involve?
Participants are randomly allocated to one of three groups. Those in group 1 are given a faecal microbiota transplant (FMT) by retention enema on one occasion. Those in group 2 are given a FMT on five consecutive days. Those in group 3 act as controls and are given bowel purgatives and antibiotic preparation and do not receive FMT. Response to the treatment is measured by endoscopic assessment at 12 weeks, patient symptom scores, blood testing, tissue biopsy and measurement of tissue inflammatory cytokine levels. The faecal bacterial profile is monitored to ensure that the transplant is durable. Donors are carefully screened for infectious diseases to minimise the risk of transmission. The results of the study will be used to plan a large scale study to establish FMT as a viable therapy in UC patients.

What are the possible benefits and risks of participating?
The benefits of participating in the trial are that patients may experience improvement in their colitis symptoms as reported in previous small studies. There is a small but theoretical risk of transmission of as yet unknown infectious disease, despite through systematic testing of donated material for known pathogens in accordance with current guidelines.

Where is the study run from?
Abertawe Bro Morgannwg University LHB (Wales)

When is the study starting and how long is it expected to run for?
September 2015 to March 2018

Who is funding the study?
NISCHR Pathway to Portfolio (Wales)

Who is the main contact?
Professor Dean Harris

Contact information

Prof Dean Harris
Scientific

Dept of Surgery
Singleton Hospital
Sketty Lane
Swansea
SA2 8QA
United Kingdom

ORCiD logoORCID ID 0000-0003-2673-8946

Study information

Study designInterventional randomised single-blind phase II trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use contact details to request a participant information sheet
Scientific titleFaecal Microbiota Transplantation in Ulcerative Colitis: an Interventional randomised single blind phase II trial
Study acronymFMTUC
Study objectivesTo estimate the magnitude of treatment response of ulcerative colitis to FMT
Ethics approval(s)Wales REC6 ethics committee, 21/09/2015, ref: 15/WA/0262
Health condition(s) or problem(s) studiedUlcerative colitis
InterventionFaecal microbiota transplant (FMT) will be administered by retention enema to patients either once only (group 1) or on five consecutive days (group 2). A third group with active disease will act as controls and receive bowel purgatives and antibiotic preparation without active administration of FMT. Randomisation to each group will be web-based.
Intervention typeOther
Primary outcome measure1. Remission of UC (mucosal healing) at 12 weeks as assessed by sigmoidoscopy, and patients response. Will also be measured utilising the Mayo scoring system for assessment of ulcerative colitis activity at 12 weeks, with remission defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0.
2. Successful engraftment of donor faecal microbiota at 12 weeks as analysed by 16S sequencing
Secondary outcome measures1. Rate of recruitment of patients
2. Disease specific severity scoring after treatment
3. Histological grading of colitis severity after treatment
4. Mucosal immunological response to treatment
5. Rate of development of adverse effects of FMT
Overall study start date01/03/2015
Completion date30/09/2020

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants30
Key inclusion criteria1. Newly diagnosed histologically confirmed ulcerative colitis with inflammation limited to the rectum or rectosigmoid (within 40cm of anal verge as measured by flexible sigmoidoscope)
2. Age 18 years and above
3. Able to give full informed written consent
4. Willing to return for sequential FMT dosing and endoscopic assessment
5. Not in receipt of standard medical treatment for colitis such as steroids or 5-ASA ie treatment naive
Key exclusion criteria1. Patients without a definitive diagnosis of UC (for example diagnosis of Crohn’s disease or infectious colitis)
2. Have colitis extending beyond 40cm from the anal verge
3. Have severe acute colitis (defined as greater than 6 bloodstained stools per 24 hrs with one of the following: pulse rate >90/ temperature >37.8’C/ haemoglobin <105g/L / ESR>30)
5. Abdominal tenderness on examination
6. Already commenced standard medical therapy for UC
7. Contraindication to oral bowel preparation
8. Allergy to study antibiotics
9. Age less than 18
10. Patient is within a vunerable group
11. Are pregnant
12. Are immuno-suppressed e.g. transplant patient
13. Known communicable disease;,at least 2 weeks full recovery from infectious disease e.g. chickenpox
14. Systemic autoimmunity, or atopic diseases
15. Previous prosthetic implant (for example metallic heart valve, joint replacement, ventriculoperitoneal shunt, cardiac stent)
16. Chronic pain syndromes (for example: fibromyalgia, chronic fatigue)
17. Neurologic, neuro-developmental or neurodegenerative disorders
18. Depression (requiring therapy)
19. Obesity (BMI>35)
20. Malignancy
21. Use of antibiotics for any indication within the past 3 months
22. Foreign travel to areas of enteric disease prevalence within 3 months
23. High risk sexual behaviour (examples: sexual contact with anyone with HIV/HTLV/AIDS or hepatitis B/C carrier, men who have sex with men (MSM))
24. Known exposure to HIV or hepatitis B/C
25. Current/previous use of injected drugs or intranasal cocaine
26. Tattooing, piercing, cosmetic botulinum toxin (Botox) or permanent makeup within 120 days (in line with Welsh Blood Transfusion guidelines)
27. Recent transfusion, transplant or skin graft
28. Risk factors for variant Creutzfeldt-Jakob disease e.g. blood transfusion or transplant after 1st January 1980
Date of first enrolment30/09/2015
Date of final enrolment31/03/2020

Locations

Countries of recruitment

  • United Kingdom

Study participating centre

Abertawe Bro Morgannwg University LHB
Port Talbot
-
United Kingdom

Sponsor information

Abertawe Bro Morgannwg University LHB (UK)
Hospital/treatment centre

R&D Department
Morriston Hospital
Swansea
SA6 6NL
Wales
United Kingdom

ROR logo "ROR" https://ror.org/04zet5t12

Funders

Funder type

Government

NISCHR Pathway to Portfolio

No information available

Results and Publications

Intention to publish date31/12/2020
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planTrial results will be published in peer-reviewed journals and presented at national and international conferences. Results will be published at the end of the trial and will be made available to trial participants.
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 18/10/2018 Yes No
HRA research summary 28/06/2023 No No

Editorial Notes

09/04/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/03/2019 to 31/03/2020
2. The overall end date was changed from 30/06/2019 to 30/09/2020
3. The intention to publish date was changed from 31/12/2019 to 31/12/2020
22/10/2018: Publication reference added.
03/08/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/03/2018 to 31/03/2019.
2. The overall trial end date was changed from 31/03/2018 to 30/06/2019.
3. The intention to publish date was added.
30/03/2016: Ethics approval information added.