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Trial registered on ANZCTR


Registration number
ACTRN12613000236796
Ethics application status
Approved
Date submitted
22/02/2013
Date registered
27/02/2013
Date last updated
25/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Faecal transplant for the treatment of active ulcerative colitis
Scientific title
In patients with mild to moderate ulcerative colitis, does faecal transplant induce clinical remission compared to placebo
Secondary ID [1] 281981 0
Nil known
Universal Trial Number (UTN)
U1111-1139-5849
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative colitis 288410 0
Condition category
Condition code
Oral and Gastrointestinal 288761 288761 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Faecal transplantation. Pre screened donor faeces will be administered to the right side of the colon via colonoscopy once followed by 2 enemas of donor faeces in the following week. The colonoscopy will usually take between 15 to 30 minutes and the enema less than 5 minutes.
Colonoscopy requires drinking bowel preparation the afternoon prior to the procedure to remove faeces from the colon. The colonoscope is a long tube with a camera on the end, that is inserted into the colon, usually under sedation. The faecal transplant is delivered down the colonoscope and into the bowel. This part of the procedure takes less than 1 minute. The enema is delivered by placing a short introducer into the rectum and delivering 150mls of fluid. This does not require bowel preparation or an anaesthetic.
Intervention code [1] 286553 0
Treatment: Other
Comparator / control treatment
The contol group will receive the standard of care for the treatment of ulcerative colitis. They will also recieve their own faeces via colonoscopy and 2 subsequent enemas as a placebo control.

Each subject potentially suitable for the study, will be asked to donate a stool sample of their own. A small portion of the stool will undergo faecal associated microbiota analysis. The remainder will be mixed with 10% sterile pharmaceutical grade glycerol, divided into 30g units and placed into frozen storage. This stool will then be used to transplant those subjects randomized to receive “placebo” with their own stool. In this way the FT will remain blinded to both the subject and colonoscopist

Standard of care for ulcerative colitis

The management of ulcerative colitis involves both maintenance medication and medication used to control flares of the disease. The goal of maintenance therapy in UC is to maintain steroid-free remission, clinically and endoscopically. This requires regular clinical assessment including history, physical examination and at times colonoscopic examination. Other tools of assessment include blood (e.g. CRP, WCC) and stool (calprotectin) testing for inflammatory markers and imaging including MRI, CT or ultrasound.

The choice of maintenance treatment in UC is determined by disease extent, disease course (frequency of flares), failure of previous maintenance treatment, severity of the most recent flare, treatment used for inducing remission during the most recent flare, safety of maintenance treatment, and cancer prevention. The mainstay of maintenance medication are the 5-aminosalicylic acid compounds (5-ASA) such as mesalazine or sulphasalazine. These compounds are commonly taken orally in formulations that predominantly deliver the active 5-ASA component to the colon. Alternatively, or in addition, mesalazine preparations can be delivered topically via enema or suppository if the disease only involves the left side of the colon (although it is only PBS funded for topical therapy during a flare and not for maintenance of remission – even though it also works in this setting). The majority of patients can be managed with maintenance 5-ASA compounds most of the time. For patients who have repeated flares of disease on 5-ASA maintenance therapy (1 or more flares in a year needing steroids), thiopurine medication such as Azathioprine or 6-mercapropurine should be used. These medications induce systemic immunosuppression, reduce the incidence and severity of flares of colitis but also slightly increase the risk of some infections and malignancy. Anti-TNF agents such as infliximab or adalimumab have been shown to have benefit in maintaining remission in UC (and are licensed for this indication by the TGA), however these agents are very expensive and not funded by the pharmaceutical benefits scheme in Australia and so, are not readily available. The anti TNF agents also give an increased risk of infection, particularly latent TB reactivation.

Mild flares of ulcerative colitis can be managed with higher doses of oral 5-ASA compounds or the addition of topical 5-ASAs given via enema or suppository. More severe flares are usually managed with a course of systemic corticosteroid. These can be given intravenously in acute, severe disease or orally in less severe flares. The steroids should then be tapered over time and discontinued. There is no indication for long term steroid use in ulcerative colitis and prolonged steroid use is associated with a number of complications including infection, osteoporosis, obesity, diabetes, poor wound healing, thinning skin, mood changes and insomnia. Severe flares of ulcerative colitis not responsive to steroids may respond to rescue therapy with the addition of either cyclosporin or anti-TNF therapy.

Patients in whom colonic inflammation cannot be controlled adequately frequently undergo total colectomy. This may be done electively (for refractory disease) or emergently in acute fulminant colitis. Colectomy entails surgical risk that is higher in the emergent setting; this risk includes infection, wound breakdown and a mortality rate. Colectomy is considered “curative” for ulcerative colitis especially if they have an ileostomy stoma created, however, it frequently also leads to complications both short- and long-term. In addition, in patients in whom a ileal-anal pouch is fashioned up to 50% of patients will subsequently develop pouchitis at 4 years post surgery.
Control group
Placebo

Outcomes
Primary outcome [1] 288898 0
Clinical and endoscopic remission (Total Mayo score less than or equal to 2 and endoscopic mayo score of less than or equal to 1)
Timepoint [1] 288898 0
8 weeks
Secondary outcome [1] 301272 0
Differences in faecal associated microbiota between donor and active UC at each time point

Patients will also give a stool sample in the week prior to their colonoscopy at 8 weeks and 12 months for faecal associated microbiota analysis. This will be compared to the faecal associated microbiota of the donor.
Timepoint [1] 301272 0
8 weeks and 12 months
Secondary outcome [2] 301273 0
Changes in mucosal and faecal associated microbiota following FT, stratified by:
1. whether FT leads to remission or not &
2. whether subjects received FT or Placebo

Colonoscopy will be undertaken at 8 weeks and 12 months post FT. Mucosal activity will be assessed with colonic biopsy for mucosal associated microbiota analysis will be taken at those times. Patients will also give a stool sample in the week prior to their colonoscopy at 8 weeks and 12 months for faecal associated microbiota analysis.
Remission will be assessed with clinical assessment, interview and colonoscopy using MAYO criteria at 8 weeks and 12 months.
Timepoint [2] 301273 0
8 weeks and 12 months
Secondary outcome [3] 301274 0
Durability of donor microbiome following FT


Colonoscopy will be undertaken at 8 weeks and 12 months post FT. Mucosal activity will be assessed with colonic biopsy for mucosal associated microbiota analysis will be taken at those times. Patients will also give a stool sample in the week prior to their colonoscopy at 8 weeks and 12 months for faecal associated microbiota analysis. These measurement of microbiome will be compared to the stool donor profile at the 2 time points.
Timepoint [3] 301274 0
8 weeks and 12 months
Secondary outcome [4] 301275 0
Changes in colonic immunological activity following FT


Colonoscopy will be undertaken at 8 weeks and 12 months post FT. Immunological activity will be assessed with colonic biopsy for Immunological analysis will be taken at those times. Patients will also undergo a blood test at the time of their colonoscopy at 8 weeks and 12 months for analysis of peripheral blood mononuclear cells.
Timepoint [4] 301275 0
8 weeks and 12 months
Secondary outcome [5] 301276 0
Patient perception and palatability

This will be assessed with a questionnaire at entry into the study and again at 12 months post faecal transplant.
Timepoint [5] 301276 0
On entry into the study and at 12 months
Secondary outcome [6] 346994 0
Clinical Remission as measured by Simple Clinical Colitis Activity Index (SCCAI) of less than or equal to 2. The SCCAI is a weekly symptom diary.
Timepoint [6] 346994 0
Week 8 and week 52
Secondary outcome [7] 346995 0
Endoscopic remission (endoscopic mayo score =0)
Timepoint [7] 346995 0
Week 8 and week 52
Secondary outcome [8] 346996 0
Clinical response (greater or equal to 3 point reduction in total mayo score)
Timepoint [8] 346996 0
Week 8
Secondary outcome [9] 346997 0
Safety. Patient reported adverse events assessed at week 8 and 1 year.
Examples of adverse events that may occur include surgical colectomy, infection, immune disease or worsening of ulcerative colitis symptoms
Timepoint [9] 346997 0
Week 8 and 1 year.

Eligibility
Key inclusion criteria
1. Mild to moderate active ulcerative colitis (total Mayo score 2 to 10)
2. Endoscopic subscore of 2 or greater (to ensure symptoms are due to UC (not post-inflammatory IBS)
3. Adult patients (aged greater than 18 years)
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severe ulcerative colitis (Mayo score 11-12 or Truelove and Witts criteria)
2. More than 25mg of prednisolone per day (or equivalent steroid)
3. Previous colonic surgery
4. Active gastrointestinal infection
5.Pregnancy
6. Anticoagulant therapy or duel antiplatelet therapy (i.e. aspirin and clopidogrel)
7. Current use of antibiotics
8. Anti-TNF therapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 605 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 606 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 10910 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [4] 10911 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 6359 0
5001 - Adelaide
Recruitment postcode(s) [2] 6360 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 286759 0
Hospital
Name [1] 286759 0
Queen Elizabeth Hospital
Private practice fund
Address [1] 286759 0
Woodville Rd,
Woodville
SA 5011
Country [1] 286759 0
Australia
Funding source category [2] 299492 0
Government body
Name [2] 299492 0
NHMRC
Address [2] 299492 0
National Health and Medical Research Council
GPO box 1421
Canberra ACT 2601
Country [2] 299492 0
Australia
Funding source category [3] 299493 0
Charities/Societies/Foundations
Name [3] 299493 0
Gutsy group
Address [3] 299493 0
Gutsy group
11 Hall St,
Hawthorn,
Victoria 3122
Country [3] 299493 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Tce,
Adelaide
SA 5005
Country
Australia
Secondary sponsor category [1] 285540 0
None
Name [1] 285540 0
Address [1] 285540 0
Country [1] 285540 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288835 0
Royal Adelaide Hospital
Ethics committee address [1] 288835 0
North Terrace
Adelaide
SA 5001
Ethics committee country [1] 288835 0
Australia
Date submitted for ethics approval [1] 288835 0
05/12/2012
Approval date [1] 288835 0
25/02/2013
Ethics approval number [1] 288835 0
121218

Summary
Brief summary
This study aims to test faecal transplant as a potential new therapy for active ulcerative colitis. Patients with ulcerative colitis have a restricted diversity of bacteria in the bowel and faecal transplant aims to replenish the diversiy of the bowel bacteria. Faecal transplant involves the delivery of stool from a faecal donor into the bowel of a patient with the aim of improving symptoms and reducing mucosal inflammation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37962 0
A/Prof Jane Andrews
Address 37962 0
Head IBD Service and Education
Department of Gastroenterology & Hepatology & School of Medicine
Royal Adelaide Hospital
North Tce
Adelaide SA 5001
Country 37962 0
Australia
Phone 37962 0
+61 8 8222 5207
Fax 37962 0
Email 37962 0
jane.andrews@health.sa.gov.au
Contact person for public queries
Name 37963 0
Dr Sam Costello
Address 37963 0
Department of Gastroenterology
Queen Elizabeth Hospital
Woodville Rd
Woodville SA 5011
Country 37963 0
Australia
Phone 37963 0
+61413311793
Fax 37963 0
Email 37963 0
sam.costello@health.sa.gov.au
Contact person for scientific queries
Name 37964 0
Dr Sam Costello
Address 37964 0
Department of Gastroenterology
Queen Elizabeth Hospital
Woodville Rd
Woodville SA 5011
Country 37964 0
Australia
Phone 37964 0
+61413311793
Fax 37964 0
Email 37964 0
sam.costello@health.sa.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary