Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001193864p
Ethics application status
Submitted, not yet approved
Date submitted
26/07/2021
Date registered
6/09/2021
Date last updated
6/09/2021
Date data sharing statement initially provided
6/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Role of Diet and Faecal Microbiota Transplantation following Bowel Cancer Surgery
Scientific title
Efficacy of Faecal Microbiota Transplantation on symptoms and Quality of Life of patients with Low Anterior Resection Syndrome
Secondary ID [1] 304876 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low Anterior Resection Syndrome 322999 0
Low Anterior Resection 323000 0
Bowel cancer 323506 0
Condition category
Condition code
Oral and Gastrointestinal 320566 320566 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Diet and Nutrition 320567 320567 0 0
Other diet and nutrition disorders
Surgery 320842 320842 0 0
Other surgery
Cancer 320843 320843 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following bowel resection due to cancer, up to 80% patients will experience variable and unpredictable bowel function and symptoms termed as Low Anterior Resection Syndrome (LARS). The exact mechanism of LARS remains unclear and currently there is no standard treatment.

This program of research will investigate if Faecal Microbiota Transplantation (FMT) can improve the bowel function and patient’s quality of life (QoL).


Phase 1- Dose-finding-study.
Group 1: FMT at one year post Ultra Low Anterior Resection (ULAR)/LAR via lower route (colonoscopy). Dose includes 4 x BiomeBoostTM FMT syringes, containing a total of 50 g of faecal matter as the active ingredient.

Group 2: FMT at one year post ULAR/LAR via lower route (colonoscopy). Dose includes 6 x BiomeBoostTM FMT syringes, containing a total of 75 g of faecal matter as the active ingredient.

FMT dose will be administered at one time, by the specialist conducting the colonoscopy (gastroenterologist/surgeon). The procedure of delivering FMT will only add 5 minutes to the routine colonoscopy being performed.

Adherence will be monitored by:
1. Dietetic phone follow up "How well did you follow the intervention" in a non judgmental format.
Intervention code [1] 321267 0
Treatment: Other
Comparator / control treatment
Group 3: Standard care, will be following their standard/normal care with no modifications.

This includes the patient following their "normal diet" and not taking any supplements such as prebiotics/probiotics that may alter the gut microbiome.
Control group
Active

Outcomes
Primary outcome [1] 328384 0
Bowel function assessed via Low Anterior Resection Syndrome (LARS) questionnaire
Timepoint [1] 328384 0
At baseline (week 0) and week 4 post intervention commencement.
Primary outcome [2] 328385 0
General quality of life (QoL) assessed via Cancer Quality of Life-general post cancer questionnaire (EORTC QLQ-C30)
Timepoint [2] 328385 0
At baseline (week 0) and week 4 post intervention commencement.
Primary outcome [3] 328641 0
Colorectal specific quality of life (QoL) assessed via Colorectal specific QoL (EORTC QLQ-C30) questionnaire
Timepoint [3] 328641 0
At baseline (week 0) and week 4 post intervention commencement.
Secondary outcome [1] 398850 0
Composite outcome of gut microbiota composition and diversity via 16S rRNA gene sequencing of a stool sample.
Timepoint [1] 398850 0
At baseline (week 0) and week 4 post intervention commencement.
Secondary outcome [2] 399797 0
Inflammation assessed via Faecal calprotectin from blood sample
Timepoint [2] 399797 0
At baseline (week 0) and week 4 post intervention commencement.
Secondary outcome [3] 399799 0
Immune response via full blood count from blood sample
Timepoint [3] 399799 0
At baseline (week 0) and week 4 post intervention commencement.

Eligibility
Key inclusion criteria
i. Ileostomy reversed with background of LAR or ULAR due to adenocarcinoma of the colon or rectum
ii. Minor or Major Low Anterior Resection Syndrome (LARS)
iii. >18 years of age
Minimum age
19 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i. Metastatic colorectal cancer (stage IV)
ii. Inflammatory Bowel Disease
iii. Patients with dementia
iv. Inability to provide informed consent
v. Permanent ileostomy/colostomy
vi. Planned for post-operative radiotherapy
vii. Autoimmune disease (uncontrolled) or on steroids (systemic) i.e. prednisolone
viii. Anaphylactic food allergy
ix. Neutropenia (<1)
x. Pregnant or breast feeding
xi. Use of probiotics, once recruited

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
All data analysis will be performed using IBM SPSS Statistics for Windows (Release 26.0, 2020; Armonk, NY: IBM Corp). The Shapiro-Wilk test will be used to test the assumption of normality along with visual check of instograms. Means and standard deviations will be presented as the descriptive statistics for normally distributed data. Medians and interquartile ranges are described for non-normal data. Categorical data will be summarised with frequencies and proportions. A mixed model ANOVA will be used to investigate impact of each intervention group on bowel symptoms and QOL scores and over four time points. Intention to treat analysis will be undertaken. The model will account for non-compliance, drop outs and other relevant confounding factors such age, gender, severity of bowel disease and others. Statistical significance will be obtained if the Bonferroni-adjusted p<0.05.

Primer7 and Permavona+ (PRIMER-E, Plymouth) will be used to analyse microbiome data (multivariate). Firstly, Principal Coordinates Analysis will be used to visualize the data, followed by distance-based linear models and redundancy analysis for a closer analysis. This will be also done to interpret findings with other data (such as Composition) which can assist in understanding the relationship between the two.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2021
Actual
Date of last participant enrolment
Anticipated
1/09/2023
Actual
Date of last data collection
Anticipated
24/11/2024
Actual
Sample size
Target
67
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 309251 0
University
Name [1] 309251 0
Edith Cowan University
Country [1] 309251 0
Australia
Primary sponsor type
University
Name
Edith Cowan University
Address
270 Joondalup Dr, Joondalup WA 6027
Country
Australia
Secondary sponsor category [1] 310219 0
Hospital
Name [1] 310219 0
Saint John of God Hospital (Subiaco)
Address [1] 310219 0
12 Salvado Rd, Subiaco WA 6008
Country [1] 310219 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 309094 0
Edith Cowan University
Ethics committee address [1] 309094 0
270 Joondalup Dr, Joondalup WA 6027
Ethics committee country [1] 309094 0
Australia
Date submitted for ethics approval [1] 309094 0
16/08/2021
Approval date [1] 309094 0
Ethics approval number [1] 309094 0
Ethics committee name [2] 309096 0
St John of God Health Care. Human Research Ethics Committee
Ethics committee address [2] 309096 0
12 Salvado Rd, Subiaco WA 6008
Ethics committee country [2] 309096 0
Australia
Date submitted for ethics approval [2] 309096 0
01/09/2021
Approval date [2] 309096 0
Ethics approval number [2] 309096 0

Summary
Brief summary
Following bowel resection due to cancer, up to 80% of patients will experience variable and unpredictable bowel function and symptoms termed as Low Anterior Resection Syndrome (LARS). The exact mechanism of LARS remains unclear and currently there is no standard treatment. Research shows that the gut microbiome, also known as gut bacteria, is changed in patents following bowel cancer and may be linked with LARS and the changes in bowel function and symptoms experienced. This program of research therefore aims to examine the effect of Faecal Microbiota Transplantation in LARS symptoms, the gut microbiome and quality-of-life.

Who is it for?
You may be eligible for this study if you are aged 19 years or older, have had an ileostomy reversed with a background of low anterior resection or ultra-low anterior resection due to adenocarcinoma of the colon or rectum, and are experiencing symptoms of minor or major LARS.

Study details
Participants will be randomised (i.e. allocated by chance) to receive one of two different doses of faecal microbiota transplant, or standard care. Faecal microbiota transplant involves administering faecal matter via a syringe using colonoscopy, which requires insertion of a flexible tube into the rectum, and will take an addition of approximately 5 minutes to your routine colonoscopy to complete. Participants allocated to standard care will not receive a faecal microbiota transplant. All participants will answer a number of questionnaires about bowel function and quality of life, and will provide a stool sample for analysis at baseline and week 4 of the study. Participants will also provide a blood sample to assess their immune response and signs of inflammation at baseline and week 4 of study.

It is hoped that this research will show that faecal microbiota transplant is an effective treatment for reducing symptoms of LARS and improving quality of life in patients who have undergone a low anterior resection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112954 0
Miss Eleonora Stojanoska
Address 112954 0
Edith Cowan University
270 Joondalup Dr, Joondalup WA 6027
Country 112954 0
Australia
Phone 112954 0
+61 411398185
Fax 112954 0
Email 112954 0
[email protected]
Contact person for public queries
Name 112955 0
Miss Eleonora Stojanoska
Address 112955 0
Eleonora Stojanoska
Edith Cowan University
270 Joondalup Dr, Joondalup WA 6027
Country 112955 0
Australia
Phone 112955 0
+61 411398185
Fax 112955 0
Email 112955 0
[email protected]
Contact person for scientific queries
Name 112956 0
Miss Eleonora Stojanoska
Address 112956 0
Eleonora Stojanoska
Edith Cowan University
270 Joondalup Dr, Joondalup WA 6027
Country 112956 0
Australia
Phone 112956 0
+61 411398185
Fax 112956 0
Email 112956 0
[email protected]

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12661Study protocol  [email protected] The study protocol may be obtained by emailing the... [More Details]



Results publications and other study-related documents

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