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Trial registered on ANZCTR


Registration number
ACTRN12621001041842
Ethics application status
Approved
Date submitted
9/06/2021
Date registered
9/08/2021
Date last updated
9/08/2021
Date data sharing statement initially provided
9/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Examining the role of faecal microbiota transplantation (FMT) to induce remission in resistant ulcerative proctitis (UP): A pilot study
Scientific title
Examining the safety and efficacy of faecal microbiota transplantation (FMT) to induce remission in resistant ulcerative proctitis (UP): A single arm prospective study
Secondary ID [1] 304305 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
UP-FMT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 322046 0
Condition category
Condition code
Oral and Gastrointestinal 319771 319771 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
- Participants who meet study inclusion criteria and provide informed consent will receive an induction course of 6 single donor FMT enemas over 8 weeks in addition to their standard therapy. FMT syringes will be administered through enemas by either trials team or self-administration at weeks 0, 1, 2, 3, 5 and 7. All FMT enemas will be administered at The Queen Elizabeth Hospital, South Australia. Each 50ml single donor FMT enema will consist of 25% stool, 65% saline and 10% glycerol. Adherence will be observed through investigator administered enemas and recording of FMT administration.
- All participants will receive a 1-week course of oral vancomycin pre-conditioning prior to FMT induction. Each participant will receive 125mg four times daily vancomycin for 7 days. This will commence 9 days prior to first dose of FMT administration to allow 48 hour washout period prior to FMT commencement. Strategies used to monitor adherence include dispensation records and direct recording.
- All participants will receive dietary advice prior to commencement of FMT enemas. This will be administered through a dietary information sheet developed by our trial dietician. This dietary information is derived from Healthy Eating for Adults brochures published by Australian Dietary Guidelines. This dietary information sheets recommends intake of resistant starches, wholegrain products, lean meats and is not specific to ulcerative colitis. Adherence to prescribed diet will be through recording of 72 hour diet diaries. Advice is based upon consensus guidelines.

Intervention code [1] 320648 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327631 0
Safety: Safety outcomes will be captured through premature study withdrawal and by a formal adverse event reporting tool designed for use in this trial. Adverse events (AEs) will be categorised as mild-moderate or serious.
Timepoint [1] 327631 0
Weekly assessment during course of study using standardised adverse event reporting tool.
Secondary outcome [1] 395990 0
Tolerability:
- Tolerability of FMT delivered via enema as assessed using a 100mm VAS at baseline, week 5 and week 8 of FMT therapy
Timepoint [1] 395990 0
Baseline, Week 5 and Week 8
Secondary outcome [2] 395991 0
Clinical remission rates of ulcerative proctitis after 8 weeks of FMT therapy as assessed by composite clinical Mayo score (including both partial and endoscopic components) of less than or equal to 2
Timepoint [2] 395991 0
Baseline, Week 8
Secondary outcome [3] 395992 0
Endoscopic Healing: Assessing Effect of FMT on endoscopic Ulcerative Colitis disease activity using Ulcerative Colitis Endoscopic Index of Severity Score (UCEIS) with endoscopic remission defined as UCEIS less than or equal to 1
Timepoint [3] 395992 0
Baseline, Week 8
Secondary outcome [4] 395994 0
Mucosal healing: Assessing effect of FMT on inducing histological remission using biopsies taken from the endoscopically worst affected areas of inflammation. Histological grading will be performed using the Robarts Histopathology Index
Timepoint [4] 395994 0
Baseline, Week 8
Secondary outcome [5] 395995 0
Patient Reported Outcomes (PROs): Assessment of median change in health related quality of life using Inflammatory Bowel Disease Questionnaire - 32 (IBDQ) following FMT therapy
Timepoint [5] 395995 0
Baseline, Week 8
Secondary outcome [6] 395996 0
Assessing change in colonic microbial composition following FMT using shotgun metagenomic sequencing of faecal samples

Timepoint [6] 395996 0
Baseline, Week 8
Secondary outcome [7] 395997 0
Change in colonic metabolic function following FMT through bacterial metabolic analysis
Timepoint [7] 395997 0
Baseline, Week 8
Secondary outcome [8] 397801 0
Assessing change in colonic microbial diversity following FMT therapy using metagenomic sequencing of faecal samples
Timepoint [8] 397801 0
Baseline, 8 weeks
Secondary outcome [9] 399101 0
Clinical Response: Improvement in UP disease activity as defined by reduction in Simple Clinical Colitis Activity Index (SCCAI) of 3 or more
Timepoint [9] 399101 0
Baseline, 8 weeks
Secondary outcome [10] 399102 0
Biochemical Response: Assessment of change in serum C-Reactive Protein (CRP) post FMT
Timepoint [10] 399102 0
Baseline, 8 weeks
Secondary outcome [11] 399317 0
Biochemical Response: Assessment of change in faecal calprotectin levels from stool samples post FMT
Timepoint [11] 399317 0
Baseline, 8 weeks

Eligibility
Key inclusion criteria
• Patients aged 18-80
• Formal diagnosis of UC for a period of greater than or equal to 3 months
• Endoscopic Assessment confirming disease activity limited to 30cm from the anal verge
• Mild-moderate UP disease activity as defined by total Clinical Mayo Score 3-10 with a Mayo endoscopic sub-score greater than 0
• Prior histological assessment consistent with UC
• Current or prior use of either oral or topical 5-ASA therapy
• Participants on stable therapy for defined periods:
o No therapy for 4 weeks prior to study commencement, or
o Stable doses of topical and/or oral 5-ASA for at least 4 weeks prior to study commencement, or
o Stable doses of corticosteroids at doses of <20mg prednisolone for 4 weeks prior to study commencement, or
o Stable doses of immunomodulator (azathioprine, mercaptopurine) for 6 weeks prior to study commencement, or
o Stable doses of biological therapy for 8 weeks prior to study commencement
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• <18 years or >80 years of age
• Quiescent UP activity as defined by total Clinical Mayo Score of < 3 and/or Mayo endoscopic sub-score of 0
• Severe UP as defined by total Clinical Mayo Score > 10 and/or evidence of systemic toxicity as defined by Truelove and Witts Criteria (Heart Rate > 90, fever > 37.8C, ESR >30, Hb <110)
• Participants with histological diagnosis consistent with Crohn’s Disease
• Participants with evidence of active infection of current/recent use of antibiotics within 1 month of enrolment
• Participants currently receiving corticosteroids at doses of >20mg prednisolone or any IV corticosteroids
• Participants who have undergone prior colonic surgery
• Participants who are unable to provide informed consent
• Participants who are pregnant or breast-feeding
• Participants who are currently enrolled in any other clinical trial
• Participants who have had any HIV or viral hepatitis exposure in the last 12 months
• Participants with a family history of colorectal carcinoma involving two or more first-degree relatives
• Participants who have an active malignancy
• Participants with current history of intravenous drug use
• Participants with liver cirrhosis or primary sclerosing cholangitis
• Participants with significant psychiatric or medical co-morbidities

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety
Statistical methods / analysis
With regards to sample size, previous RCTs of FMT in UC have demonstrated moderate-severe adverse event rates of 0-13%. Estimating a moderate-severe adverse event rate of 13% will allow us to identify significant adverse events from FMT with a sample size of 21 patients at 95% confidence level. An RCT analysing effect of FMT on remission induction conducted at TQEH experienced a dropout percentage of 7.9% (3/38 patients) in the treatment group. Similarly, we would expect dropout rates to be less than 20% ensuring at least 21 participants in this pilot study.

Baseline demographic, clinical and dietary factors will be presented using means (standard deviation), medians (inter-quartile range) or frequencies (percentages) as appropriate. Safety and tolerability data will be presented using means (standard deviation), medians (inter-quartile range) or frequencies (percentages) as appropriate. Multivariable regression analysis will be performed to assess factors associated with clinical and endoscopic remission. Microbiome analysis will measure diversity (both alpha and beta diversity) and computational methods will be utilised to identify organisms associated with remission.

Recruitment
Recruitment status
Not yet recruiting
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)
NSW,NT,SA
Recruitment hospital [1] 19526 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [2] 19527 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 19528 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 19529 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [5] 19530 0
Broken Hill Base Hospital - Broken Hill
Recruitment hospital [6] 19531 0
Alice Springs Hospital - Alice Springs
Recruitment postcode(s) [1] 34135 0
5011 - Woodville
Recruitment postcode(s) [2] 34136 0
5000 - Adelaide
Recruitment postcode(s) [3] 34137 0
5042 - Bedford Park
Recruitment postcode(s) [4] 34138 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 34139 0
2880 - Broken Hill
Recruitment postcode(s) [6] 34140 0
0870 - Alice Springs

Funding & Sponsors
Funding source category [1] 308680 0
Hospital
Name [1] 308680 0
The Queen Elizabeth Hospital (TQEH) Inflammatory Bowel Disease Service
Address [1] 308680 0
TQEH IBD Service
Level 4C
TQEH
28 Woodville Road
Woodville South
SA 5011
Country [1] 308680 0
Australia
Primary sponsor type
Government body
Name
Central Adelaide Local Health Network (CALHN)
Address
CALHN Research Services
SA Health
Level 3, Roma Mitchell Building
136 North Terrace, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 309560 0
None
Name [1] 309560 0
Address [1] 309560 0
Country [1] 309560 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308602 0
Central Adelaide Health Network (CALHN) Human Research Ethics Committee (HREC)
Ethics committee address [1] 308602 0
CALHN Research Services
Central Adelaide Local Health Network Inc.
SA Health
Level 3, Roma Mitchell Building
136 North Terrace, Adelaide, SA 5000


Ethics committee country [1] 308602 0
Australia
Date submitted for ethics approval [1] 308602 0
04/03/2021
Approval date [1] 308602 0
27/04/2021
Ethics approval number [1] 308602 0
2021/HRE00088

Summary
Brief summary
This single-centre single arm prospective pilot clinical study aims to demonstrate the safety of donor FMT in patients with UP resistant to 5-ASA therapy. Participants who meet study inclusion criteria and provide informed consent will receive an induction course of 6 single donor FMT enemas over 8 weeks in addition to their standard therapy. All participants will receive a 1-week course of oral vancomycin pre-conditioning prior to FMT induction. Flexible sigmoidoscopy, 3-day diet diary, stool and blood panels will be performed prior to and upon completion of FMT enema induction course. This study will primarily assess the safety of FMT enemas in patients with UP. Our study will also assess the impact of FMT induction therapy on UP disease activity utilising clinical, endoscopic, histological and patient reported outcome measures. Changes in colonic microbial composition, diversity and function post FMT therapy will be analysed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111290 0
Dr Sreecanth Raja
Address 111290 0
Level 4C
TQEH IBD Service
TQEH
28 Woodville Road
Woodville South
SA 5011
Country 111290 0
Australia
Phone 111290 0
+61 8 8222 8984
Fax 111290 0
Email 111290 0
sreecanth.raja@sa.gov.au
Contact person for public queries
Name 111291 0
Dr Sreecanth Raja
Address 111291 0
Level 4C
TQEH IBD Service
TQEH
28 Woodville Road
Woodville South
SA 5011
Country 111291 0
Australia
Phone 111291 0
+61 8 8222 8984
Fax 111291 0
Email 111291 0
sreecanth.raja@sa.gov.au
Contact person for scientific queries
Name 111292 0
Dr Sreecanth Raja
Address 111292 0
Level 4C
TQEH IBD Service
TQEH
28 Woodville Road
Woodville South
SA 5011
Country 111292 0
Australia
Phone 111292 0
+61 8 8222 8984
Fax 111292 0
Email 111292 0
sreecanth.raja@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 11752 0
Study protocol
Citation [1] 11752 0
Link [1] 11752 0
Email [1] 11752 0
sreecanth.raja@sa.gov.au
Other [1] 11752 0
Type [2] 11754 0
Informed consent form
Citation [2] 11754 0
Link [2] 11754 0
Email [2] 11754 0
sreecanth.raja@sa.gov.au
Other [2] 11754 0
Type [3] 11755 0
Ethical approval
Citation [3] 11755 0
Link [3] 11755 0
Email [3] 11755 0
sreecanth.raja@sa.gov.au
Other [3] 11755 0
Summary results
No Results