Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001434785
Ethics application status
Approved
Date submitted
20/04/2022
Date registered
8/11/2022
Date last updated
8/11/2022
Date data sharing statement initially provided
8/11/2022
Date results information initially provided
8/11/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Maintaining Remission of Ulcerative Colitis with
Faecal Microbiota Transplantation: the MR-UC-FMT Trial
Scientific title
Maintaining Remission of Ulcerative Colitis with
Faecal Microbiota Transplantation: the MR-UC-FMT Trial
Secondary ID [1] 303767 0
Nil Known
Universal Trial Number (UTN)
U1111-1234-2642
Trial acronym
MR-UC-FMT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 322472 0
Inflammatory Bowel Disease 322473 0
Condition category
Condition code
Oral and Gastrointestinal 320113 320113 0 0
Inflammatory bowel disease
Inflammatory and Immune System 320114 320114 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients will receive Prednisolone 50mg oral tablet daily for Week 1, Prednisolone 37.5mg oral tablet daily for Week 2, Prednisolone 25mg oral tablet daily for Week 3 and 4, Prednisolone 20mg oral tablet daily for week 5, Prednisolone 15mg oral tablet daily for Week 6, Prednisolone 10mg oral tablet daily for Week 7 and Prednisolone 5mg daily oral tablet for Week 8 then cease.
Faecal Microbial Transplantation (FMT) is anaerobically prepared blended donor stool with 65% normal saline and 10% glycerol.
FMT administered 200mL into the caecum via colonoscopy (duration of procedure of 20 minutes, patient to remain on right side for a further 60 minutes in recovery to help retain FMT) by accredited gastroenterologist after 4 weeks of Prednisolone therapy once on Day 1 of Week 5.
Administered FMT 60mL into rectum via enema administered by gastroenterologist or gastroenterology registrar by syringe on two non-consecutive days (eg Day 4+6 or Day 5+7) following the colonoscopic FMT during week 5. Days given depend on patient and proceduralist availability. Patient to remain prone for at least 30 minutes post insertion of FMT enema, and encouraged to defer opening bowels as long as comfortable.
If in remission (defined as Mayo score less than or equal to 2 with no individual subscore greater than 1) or had an adequate clinical response (reduction in Total Mayo score of greater than or equal to 30% and 3points or more, as well as a reduction in the rectal bleeding score of greater than or equal to 1 or a rectal bleeding score of 0 or 1) at week 12, patients enter Phase 2 which begins at week 13. They will be openly randomised.
There is no placebo group.
Intervention group receives 60mL FMT enema 4 weekly for 9 months.
Patients who are not deemed to be in remission at week 12 will be discharged from the study back to their referring Gastroenterologist for treatment outside the scope of the trial.
Enemas are administered by proceduralist to ensure adherence.
Adherence to Prednisolone is assessed with verbal checks with patient prior to commencing, and at 4 and 8 week interviews. During phase 2, if flare occurs patient to be referred to Gastroenterologist to discussion around escalation of treatment, however no further prednisolone is prescribed as a routine part of phase 2.
Intervention code [1] 320930 0
Treatment: Drugs
Intervention code [2] 320931 0
Treatment: Other
Comparator / control treatment
All patients receive the same treatment in Phase 1 (first 12 weeks).
If in remission (defined as Mayo score less than or equal to 2 with no individual subscore greater than 1) or had an adequate clinical response (reduction in Total Mayo score of greater than or equal to 30% and 3points or more, as well as a reduction in the rectal bleeding score of greater than or equal to 1 or a rectal bleeding score of 0 or 1) at week 12, patients enter Phase 2 which begins at week 13. They will be openly randomised.
In Phase 2, comparator group receive 60mL enema FMT every 8 weeks for 9 months.
Control group
Dose comparison

Outcomes
Primary outcome [1] 327992 0
Measure the similarity of the donor Faecal Microbiota Transplant (FMT) to the Ulcerative Colitis (UC) recipient stool sample microbiota and compare between 4-weekly and 8-weekly doses using unweighted UniFrac, Jensen-Shannon distance and Prinicipal Components Anaylsis (PCA).
Timepoint [1] 327992 0
Four weekly from week 12 to week 52 post commencement of prednisolone (8 to 48 weeks post Colonoscopic FMT). The primary timepoint is Week 52 (48 weeks post Colonoscopic FMT).
Primary outcome [2] 327993 0
Compare the alpha diversity of UC recipients’ stool sample microbiota using Shannon and Simpson diversity, richness and evenness and PCA as well as the relative abundance of UC recipient taxonomic groups including phyla, order, genera, class and family.
Timepoint [2] 327993 0
Four weekly from week 12 to week 52 post commencement of prednisolone (8 to 48 weeks post Colonoscopic FMT). The primary timepoint is Week 52 (48 weeks post Colonoscopic FMT).
Primary outcome [3] 327994 0
Safety and tolerability of FMT by enema every 4 or every 8 weeks in patients with UC using Directed Side Effect Questionnaires (created especially for this trial).
Timepoint [3] 327994 0
Survey administered 4-weekly from week 5 to week 52 post commencement of prednisolone (week 1 to week 48 post colonoscopic FMT). The primary timepoint is Week 52 (48 weeks post Colonoscopic FMT).
Secondary outcome [1] 397176 0
Time to first flare (flare defined as Simple Clinical Colitis Activity Index (SCCAI) >4 with a Blood Score>0 as reported by the patient from observations of their bowel actions) post induction of remission in weeks comparing 4-weekly and 8-weekly groups.
Timepoint [1] 397176 0
Accessed 4 weekly from Week 12 to Week 52 post commencement of prednisolone (8 to 48 weeks post Colonoscopic FMT).
Secondary outcome [2] 397177 0
Total number of weeks in flare (flare defined as SCCAI>4 with a Blood Score>0 as reported by the patient from observations of their bowel actions) comparing 4-weekly and 8-weekly groups.
Timepoint [2] 397177 0
Accessed 4 weekly from Week 12 to Week 52 post commencement of prednisolone (8 to 48 weeks post Colonoscopic FMT).
Secondary outcome [3] 397178 0
Clinical remission defined as SCCAI <3 comparing 4-weekly and 8-weekly groups.
Timepoint [3] 397178 0
Week 28 and Week 52 post commencement of prednisolone (24 weeks and 48 weeks post Colonoscopic FMT).
Secondary outcome [4] 408948 0
Clinical endoscopic remission defined as Mayo of 2 or less with no subscore >1 comparing 4-weekly and 8-weekly groups.
Timepoint [4] 408948 0
Week 52 post commencing prednisolone (48 weeks post Colonoscopic FMT).
Secondary outcome [5] 408949 0
Clinical Response defined as a reduction in Total Mayo score of 30% or more and 3 or more points, reduction rectal bleeding of 1 or more, or score 0 or 1.
Timepoint [5] 408949 0
Week 28 and Week 52 post commencing prednisolone (24 weeks and 48 weeks post Colonoscopic FMT).
Secondary outcome [6] 415348 0
*PRIMARY OUTCOME #4
Beta Diversity of stool samples from patients in the 4 weekly and 8 weekly groups using Bray-Curtis dissimilarity.
Timepoint [6] 415348 0
Four weekly from week 12 to week 52 post commencement of prednisolone (8 to 48 weeks post Colonoscopic FMT). The primary timepoint is Week 52 (48 weeks post Colonoscopic FMT).

Eligibility
Key inclusion criteria
Patients aged 18 - 75 years
Formal diagnosis of UC for greater than or equal to 1 month
Currently under the care of a gastroenterologist
Mild to Moderately Active UC with Total Mayo score 3 to 10 inclusive.
Mayo Endoscopic Sub Score greater than or equal to 2 (to ensure symptoms are due to UC and not due to a concurrent functional bowel disorder)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe UC with Total Mayo score of greater than or equal to 11 or by Truelove Witts Criteria
Diminished mental capacity preventing consent
Pregnancy
Surgical resection of any part of the intestine
Anticoagulation or dual antiplatelet use
Antibiotic use at time of enrolment
Contraindications to the use of prednisolone (e.g. poorly controlled Diabetes Mellitus, history of steroid-induced mental health complications such as depression, mania or psychosis)
Plans for travel from South Australia for >4 weeks during the 12 months study period

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)
Allocation not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a random number generator at www.random.org.
Min 1 Max 2, 1 = 4 week group, 2 = 8 week group.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase 1 is a single group assignment, where all participants receive the same treatment for the first 12 weeks.
Phase 2 is a parallel assignment. Patients who demonstrate adequate response at Week 12 will be openly randomised to receive FMT either 4 weekly or 8 weekly.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
To measure alpha diversity (the diversity within each patient’s microbiome) we will use Shannon diversity indices. For beta diversity (the diversity collectively among the patients before and after the interventions) we will be using Bray-Curtis dissimilarity.
Similarity between the FMT and the patient biome will be calculated using unweighted Uni-Frac,Jensen-Shannon distance and PCA.
Clinical outcomes will be analysed under consultation with professional statistician depending on number of participants recruited.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Other reasons/comments
Other reasons
COVID pandemic
Date of first participant enrolment
Anticipated
Actual
25/03/2019
Date of last participant enrolment
Anticipated
Actual
31/01/2020
Date of last data collection
Anticipated
Actual
4/02/2021
Sample size
Target
60
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 22225 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 37387 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 308172 0
University
Name [1] 308172 0
University of Adelaide
Country [1] 308172 0
Australia
Funding source category [2] 311286 0
Commercial sector/Industry
Name [2] 311286 0
BiomeBank
Country [2] 311286 0
Australia
Funding source category [3] 311287 0
Hospital
Name [3] 311287 0
The Queen Elizabeth Hospital
Country [3] 311287 0
Australia
Primary sponsor type
Hospital
Name
Central Adelaide Local Health Network
Address
Department of Gastroenterology and Hepatology
4B, Level 4 Towel Block
The Queen Elizabeth Hospital
28 Woodville Road, Woodville South South Australia 5011
Country
Australia
Secondary sponsor category [1] 308943 0
University
Name [1] 308943 0
University of Adelaide
Address [1] 308943 0
School Of Public Health
University Of Adelaide
57 North Terrace, Adelaide SA 5000
AUSTRALIA
Country [1] 308943 0
Australia
Secondary sponsor category [2] 314143 0
University
Name [2] 314143 0
Biomebank
Address [2] 314143 0
2 Ann Nelson Dr, Thebarton SA 5031
Country [2] 314143 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308157 0
Central Adelaide Local Health Network Research Ethics Committee
Ethics committee address [1] 308157 0
Royal Adelaide Hospital
Clinical Trial Centre
Wayfinder 3D460.02
Level 3
Port Road
ADELAIDE SA 5000
Ethics committee country [1] 308157 0
Australia
Date submitted for ethics approval [1] 308157 0
21/09/2018
Approval date [1] 308157 0
08/12/2018
Ethics approval number [1] 308157 0
HREC/18/CALHN/646

Summary
Brief summary
Maintenance of Remission for Ulcerative Colitis with Faecal Microbiota Transplantation; the MR-UC-FMT trial is prospective clinical trial designed to determine the dosing interval of Faecal Microbiota Transplantation administered by enema with a view to maintain remission following induction with FMT and prednisolone.
The study recruits patients with mild to moderate Ulcerative Colitis and enrols them into two phases of the trial. The first phase involves an 8 week course of prednisolone with a Faecal Microbiota Transplantation given via colonosopy at week 5 with a view to induce remission or adequate clinical response.
Those patients who respond to treatment will be openly randomised to receive FMT via clinician administered enema every 4 or 8 weeks for a further 40 weeks (total 52 weeks).
The study aims to test the hypothesis that:
-FMT given more frequently via enema is more likely to result in the patient's microbiome becoming more similar to the FMT than the patient's baseline microbiome.
-The therapeutic effect of FMT is that the bacteria in the patient's colon become the same as those in the transplant material.
-The therapeutic effect of FMT is to improve the diversity of bacteria in the patient's colon
-FMT is more effective if given with prednisolone for induction of remission.
-FMT given more frequently improves outcomes including time to flare, weeks in flare and clinical or endoscopic remission at 28 and 52 weeks.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109734 0
Dr Karmen Telfer
Address 109734 0
Department of Gastroenterology and Hepatology
4B, Level 4 Tower Block
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South
SA 5011 AUSTRALIA
Country 109734 0
Australia
Phone 109734 0
+61 421174684
Fax 109734 0
Email 109734 0
karmen.telfer@gmail.com
Contact person for public queries
Name 109735 0
Dr Karmen Telfer
Address 109735 0
Department of Gastroenterology and Hepatology
4B, Level 4 Tower Block
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South
SA 5011 AUSTRALIA
Country 109735 0
Australia
Phone 109735 0
+61 421174684
Fax 109735 0
Email 109735 0
karmen.telfer@gmail.com
Contact person for scientific queries
Name 109736 0
Dr Karmen Telfer
Address 109736 0
Department of Gastroenterology and Hepatology
4B, Level 4 Tower Block
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South
SA 5011 AUSTRALIA
Country 109736 0
Australia
Phone 109736 0
+61 421174684
Fax 109736 0
Email 109736 0
karmen.telfer@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
To maintain patient confidentiality given the small number of participants in the trial.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.