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Trial registered on ANZCTR


Registration number
ACTRN12621000234819p
Ethics application status
Submitted, not yet approved
Date submitted
14/11/2020
Date registered
5/03/2021
Date last updated
5/03/2021
Date data sharing statement initially provided
5/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Synbiotics on Gastrointestinal Chemotherapy Symptoms
Scientific title
The Efficacy of Synbiotics on Gastrointestinal Chemotherapy Symptoms in Patients with Solid Tumours: A randomised-crossover double-blinded placebo-controlled clinical trial (Pilot Study)
Secondary ID [1] 302691 0
None
Universal Trial Number (UTN)
Trial acronym
SYNAGICS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid tumours 319607 0
Condition category
Condition code
Cancer 317563 317563 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Synbiotic formulation (combination of prebiotic and probiotic) will be used in this pilot study. The study synbiotic formulation consists of prebiotic sugarcane flour and Bacillus Coagulans (probiotic). One dose of formulation contains Bacillus coagulans spores 2 Billion CFU and 1.5g prebiotic sugar cane flour.
This study will recruit 40 participants and will be randomly allocated into two groups receiving synbiotic treatment or placebo in different order during their chemotherapy treatment. Patients receiving chemotherapy typically undergo several 4-week cycles of treatment. Therefore, group 1 will receive the synbiotic preparation for the first two weeks of their first chemotherapy cycle, followed by a washout period in the third and fourth week of the cycle. During the first two weeks of the second chemotherapy cycle group 1 will receive the placebo followed again, by two weeks of washout. This sequence will be repeated for the third and fourth chemotherapy cycles. Group 2 will receive the placebo in the first chemotherapy cycle followed by wash out and the synbiotic preparation in second chemotherapy cycle, this sequence will repeat in the third and fourth cycles.
The synbiotic formulation will be taken by mouth twice daily for two weeks from commencement of chemotherapy cycle. Participants will be instructed by a research Nurse on how to consume the synbiotic formulation/placebo. Participants need to stir one sachet of synbiotics formulation or placebo into a glass of water and consume 30 minutes before food each morning and night, ensuring it is consumed immediately in suspended form.

The study participants will be asked to return the empty sachets along with the questionnaires in order to monitor the adherence of the intervention.
Intervention code [1] 319002 0
Prevention
Intervention code [2] 319366 0
Lifestyle
Comparator / control treatment
The participants will be randomly allocated into two groups receiving synbiotic treatment or placebo in different order during their chemotherapy treatment. Group 1 will receive the synbiotic preparation for the first two weeks of their first chemotherapy cycle, followed by a washout period in the third and fourth week of the cycle. During the first two weeks of the second chemotherapy cycle group 1 will receive the placebo followed again, by two weeks of washout. This sequence will be repeated for the third and fourth chemotherapy cycles. Group 2 will receive the placebo in the first chemotherapy cycle followed by wash out and the synbiotic preparation in second chemotherapy cycle, this sequence will repeat in the third and fourth cycles.

Similar looking and tasting 1.5 g placebo (regenerated cellulose fibre) ingredient will be used. This will also be taken by mouth twice daily for two weeks from commencement of chemotherapy cycle.
Control group
Placebo

Outcomes
Primary outcome [1] 325623 0
Incidence and severity of chemotherapy induced gastrointestinal (GI) complications such as vomiting, diarrhoea, constipation, mucositis and other symptoms such as chest pain, dyspnoea, fatigue etc.
This is a composite primary outcome measurable as change in FACT-C scores.
Timepoint [1] 325623 0
1. Baseline (before chemotherapy).
2. Two weeks post each chemotherapy cycle.
3. At four weeks post each chemotherapy cycle.
Primary outcome [2] 325624 0
Quality of life will be assessed using the FACT-C questionnaire. FACT-C is a well-being questionnaire which includes questions about the patient’s physical, social, emotional and functional well-being as well as colorectal symptoms including diarrhoea on a scale of 0 to 4.
Timepoint [2] 325624 0
1. Baseline (before chemotherapy).
2. Two weeks post each chemotherapy cycle.
3. At four weeks post each chemotherapy cycle.
Secondary outcome [1] 388595 0
Number of patients that discontinued chemotherapy due to diarrhoea. This data will be accessed through patient medical records.
Timepoint [1] 388595 0
1. Two weeks post each chemotherapy cycle.
2. At four weeks post each chemotherapy cycle.
Secondary outcome [2] 390096 0
LPS levels will be measured by using serum assays.
Timepoint [2] 390096 0
1. Baseline (before chemotherapy).
2. Two weeks post each chemotherapy cycle.
3. At four weeks post each chemotherapy cycle.
Secondary outcome [3] 390097 0
Bristol stool score (change in stool consistency).
Timepoint [3] 390097 0
1. Baseline (before chemotherapy).
2. Two weeks post each chemotherapy cycle.
3. At four weeks post each chemotherapy cycle.

Eligibility
Key inclusion criteria
• Adult patients with solid tumour cancers starting chemotherapy treatment.
• Age range: 50-75 years, with a life expectancy of more than 12 months.
• Able to take food and fluid orally.
• Able to comply with all study requirements.
Minimum age
50 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Active infection treated by antibiotic therapy.
• Ileostomy.
• Hypersensitivity to study synbiotics.
• History of major psychiatric illness
• Any significant psychological, familial, sociological or geographical conditions, which could potentially hamper compliance with study protocol and follow-up schedule.
• Participants with low English proficiency.

Study design
Purpose of the study
Prevention
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
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
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
1. This is a double blinded randomised control trial. The results will be repeated measures, quantitative as well as descriptive and will include stool consistency scores and use of anti-diarrhoeal medication documented. The daily Bristol stool score will be the mean of all the daily assessments. The change in mean stool scores from baseline to the end of treatment will be analysed using repeated measures mixed effects general linear modelling adjusted for order and period effects. In addition, the change from baseline in mean lipopolysaccharide (LPS) levels will be analysed using repeated measures mixed effects general linear modelling (with logarithmic transformation where appropriate).
2. Rates of events (e.g. adverse, or symptom-control medication) will be estimated using Poisson regression, both comparing active treatment with placebo, and the change in event rates across the four chemotherapy treatments.
3. The data from FACT-C questionnaires (modified) will be used to measure symptom improvement using Likert scale. Differences in the distribution of symptoms between active and placebo treatment will be estimated using repeated measures ordered logistic regression adjusted for order and period effects.
4. The results will be analysed on an intention-to-treat basis. Missing data will be substituted by multiple imputation.
5. The results will be explored to identify potential confounding variables, for inclusion in the definitive randomised controlled trial.
6. At the end of the pilot study, the rate of adverse events and severity of symptoms will be used to calculate the minimum numbers of patients that would be required in a definitive randomised controlled trial examining this clinical question.

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)
TAS
Recruitment hospital [1] 17973 0
Mersey Community Hospital - Latrobe
Recruitment postcode(s) [1] 31928 0
7307 - Latrobe

Funding & Sponsors
Funding source category [1] 307127 0
Commercial sector/Industry
Name [1] 307127 0
KFSU Pty Ltd (HFS Pty Ltd now)
Address [1] 307127 0
PO Box 973, Ayr,
Queensland,
4807
Country [1] 307127 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
KFSU Pty Ltd
Address
PO Box 973, Ayr,
Queensland,
4807
Country
Australia
Secondary sponsor category [1] 307703 0
University
Name [1] 307703 0
University of Tasmania
Address [1] 307703 0
Newnham Dr,
Newnham
TAS 7248
Country [1] 307703 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307239 0
Tasmania Health and Medical Human Research Ethics Committee HREC
Ethics committee address [1] 307239 0
Office of Research Services
Private Bag 1
Hobart TAS 7001
Ethics committee country [1] 307239 0
Australia
Date submitted for ethics approval [1] 307239 0
29/08/2020
Approval date [1] 307239 0
Ethics approval number [1] 307239 0

Summary
Brief summary
This study is aiming to explore the effect of a synbiotic formulation (combination of prebiotic and probiotic) on gastrointestinal chemotherapy symptoms in patients with solid tumours.

Who is it for?
You may be eligible for this study if you are aged 50 to 75 years old, have a solid tumour cancer, and are starting chemotherapy treatment.

Study details
Study participants will be randomly allocated (by chance) to one of two arms. One group will receive a synbiotic formulation taken twice daily for two weeks at the start of the first chemotherapy cycle, while the other group receives a placebo formulation taken twice daily for two weeks at the start of the first chemotherapy cycle. After a two week break from treatment, a second chemotherapy round will take place, with group one given a placebo formulation and group two given a synbiotic formulation. This sequence will repeat in the third and fourth chemotherapy cycles.

Incidence and severity of gastrointestinal symptoms will be monitored using FACT-C questionnaire , Bristol stool score and LPS assay.

We hope that this research will improve health outcomes such as gastrointestinal symptoms alleviation from chemotherapy and better tolerability of chemotherapy leading to improved quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106522 0
Dr Krishna Kalpurath
Address 106522 0
Mersey Community Hospital
Torquay Road, Latrobe. TAS -7307
Country 106522 0
Australia
Phone 106522 0
+61 3 63485122
Fax 106522 0
+613 64265523
Email 106522 0
krishna.kalpurath@ths.tas.gov.au
Contact person for public queries
Name 106523 0
A/Prof Raj Eri
Address 106523 0
School of Health Sciences, Locked Bag 1322, LAUNCESTON TAS 7250
Country 106523 0
Australia
Phone 106523 0
+61363245467
Fax 106523 0
+6136324 5555
Email 106523 0
rderi@utas.edu.au
Contact person for scientific queries
Name 106524 0
A/Prof Raj Eri
Address 106524 0
School of Health Sciences, Locked Bag 1322, LAUNCESTON TAS 7250
Country 106524 0
Australia
Phone 106524 0
+61363245467
Fax 106524 0
+6136324 5555
Email 106524 0
rderi@utas.edu.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
Ethical approval
Other
'Other' documents specified
Research Diary including FACT-C questionaire
How or where can supporting documents be obtained?
Type [1] 9663 0
Study protocol
Citation [1] 9663 0
Link [1] 9663 0
Email [1] 9663 0
Other [1] 9663 0
Study Protocol attached
Type [2] 9664 0
Ethical approval
Citation [2] 9664 0
Link [2] 9664 0
Email [2] 9664 0
Other [2] 9664 0
We have just rebutted a set of questions from the ethics approval committee and approval is likely to be obtained in the next three to four weeks.
Attachment [2] 9664 0
Type [3] 9737 0
Other
Citation [3] 9737 0
Link [3] 9737 0
Email [3] 9737 0
Other [3] 9737 0
Research Diary
Summary results
No Results