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Trial registered on ANZCTR


Registration number
ACTRN12619000442101
Ethics application status
Approved
Date submitted
11/03/2019
Date registered
18/03/2019
Date last updated
15/12/2022
Date data sharing statement initially provided
18/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
SYMBIOTiC Study – SYMptom, microBIOme and dieT in Chronic Kidney Disease
Scientific title
A randomised, cross-over, pilot trial investigating the effects of a novel renal dietary intervention (rich in plant foods, utilising a whole food dietary approach) designed to improve diet quality, symptom burden, the gastrointestinal microbiome and other health outcomes including biochemical markers in adults with moderate to severe chronic kidney disease.
Secondary ID [1] 297153 0
Nil known
Universal Trial Number (UTN)
U1111-1227-1769
Trial acronym
SYMBIOTiC Study – SYMptom, microBIOme and dieT in Chronic Kidney Disease
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Chronic Kidney Disease 311182 0
Symptom burden 311184 0
Quality of life 311185 0
Uraemic syndrome 311186 0
Condition category
Condition code
Renal and Urogenital 309806 309806 0 0
Kidney disease
Diet and Nutrition 309807 309807 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This research will intentionally recruit people with moderate to severe, pre-dialysis chronic kidney disease (stage 3-4, eGFR 15-59mL/1.73m2) or anyone deemed suitable by the medical team (Nephrologists).

The use of a crossover trial requires fewer subjects, allows subjects to be their own controls and accounts for inter-individual variability in responses, thereby providing for a stronger study design.

Participants will be randomly allocated to either the 'intervention treatment' or 'control treatment' for the first study arm (see below in the comparator/control treatment for more information regarding the control diet). Dietary education will be based on the Evidence Based Practice Guidelines for the Nutritional Management of Chronic Kidney Disease relevant for the disease stage. For instance, education counselling for both groups will control for adequate protein and energy as well as co-morbidities that contribute to the progression of the disease (i.e. blood glucose control in diabetes, fluid and sodium control in hypertension, lipid and weight control based on the priorities relevant to the individual).

When allocated to the intervention treatment, participants will receive diet counselling and an individualised prescription for achieving at least 30 different plant foods over a 7 day (week) period as well as written information sheets designed specifically for this study. This prescription is based on new evidence and inspired by the recent findings from the American Gut Project, which is one of the largest studies to date to investigate reported habitual diets and the gut microbiome (although not specific to people with CKD). Results from this study indicated that individuals who consumed more than 30 different plant types per week, had greater gut microbiota biodiversity and reduced abundance of antibiotic resistance genes in their microbiome compared to those that consumed less than 10 plant foods per week.

Participants will first be asked to select 30 different plant foods to focus on during the first week. Following this, participants will be given an ideal day example that reflects their typical eating pattern (breakfast, lunch, dinner and snacks) but provides the number of food servings they need to consume in order to adhere to the dietary guidelines (i.e. 5 vegetable serves, two servings of fruits, 1 serve of dairy food etc.). Participants will be encouraged to swap out different plant foods from the day example using the 30 different plant foods they had individually selected to ensure they consume these foods over the week. In addition, participants will also be given a one A4 page swap-list of different plant foods and suggested serving size they can alternate over the 6 weeks to encourage variety and ensure they don't get tired of eating the same foods. Depending on the individual, specific daily targets maybe suggested to achieve the overarching goal of consuming 30 different plant foods over the week. For instance, participants may be prescribed to consume 4 different plant foods each weekday for 5 days of the week, and 5 different plant foods on weekends or at least two days over the week. A weekly checklist system for the participant to ‘tick’ or 'cross off' if they have or haven’t completed their overall targets (30 or more) for plant food consumption.

Participants will be asked to bring this check list to clinic visits/ dietetic consultations as a means to assess compliance, but also provide an opportunity for the participant and dietitian to discuss additional strategies.

Adherence to a stable diet will be monitored using 24hr food recalls at weeks 3 and 13 for both groups (the intervention and control).
Intervention code [1] 313415 0
Lifestyle
Intervention code [2] 313943 0
Treatment: Other
Comparator / control treatment
When allocated to the control treatment, participants will receive diet counselling and an individualised prescription for achieving less than 15 different plant foods over a 7 day (week) period as well as written information sheets designed specifically for this study (similar to that provided in the intervention arm).

Similar to the intervention treatment, participants will asked to highlight/ select 10-15 different plant foods to focus on during the first week of the control treatment arm. Following this, participants will be given an ideal day example that reflects their typical eating pattern structured as breakfast, lunch, dinner and snacks, but still provides the number of food servings they need to consume in order to adhere to the dietary guidelines (i.e. 5 vegetable serves, two servings of fruits, 1 serve of dairy foods or alternatives etc.). Participants will be encouraged to swap out different plant foods from the day example with the 10-15 different plant foods they had individually selected for that week. In addition, participants will also be given a one A4 page swap-list of different plant foods and suggested serving size they can alternate over the 6 weeks to encourage variety and ensure they don't get tired of eating the same foods. It will be explained to participants that the type of plant foods may differ from one week to the next; However, for that particular week period (7 days) they are asked to limit different plant foods to the suggested target of 10-15. Same as the intervention group, a weekly checklist system for the participant to ‘tick’ if they have or haven’t completed their overall targets (less than 15) for plant food consumption.

Participants who receive the intervention first, will receive a 4 week wash-out period where they can resume their 'usual' (habitual) diet. Then, participants will be encouraged to adhere to the targets of the control treatment as much as possible for the next 6 weeks in order to see if there is a change.
Control group
Active

Outcomes
Primary outcome [1] 318766 0
Change in urine concentrations of at least 1 of 2 uraemic toxins (Indoxyl Sulfate and p-Cresyl Sulfate)
Timepoint [1] 318766 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Primary outcome [2] 333389 0
Change in plasma concentrations of at least 1 of 2 uraemic toxins (Indoxyl Sulfate and p-Cresyl Sulfate)
Timepoint [2] 333389 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [1] 365956 0
Changes to serum uraemic toxin concentrations (composite secondary outcome) assessed via pathology.
Timepoint [1] 365956 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [2] 368222 0
Serum potassium assessed via relevant pathology tests.
Timepoint [2] 368222 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [3] 368223 0
Faecal and plasma metabolites will be collected and assess using either targeted (i.e. fatty acids including short chain fatty acids, Trimethylamine N-oxide, amino acids) or untargeted metabolomics analysis depending on funding.
Timepoint [3] 368223 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [4] 368224 0
Metabolic acidosis (composite secondary outcome) assessed via blood bicarbonate levels from pathology and sodium bicarbonate prescription accessed via medical records.
Timepoint [4] 368224 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [5] 368225 0
Potential renal acid load (PRAL) will be calculated using formula from diet data obtained from diet histories
Timepoint [5] 368225 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [6] 368227 0
Changes to blood lipid profiles (composite secondary outcome) including total cholesterol, LDL cholesterol, HDL cholesterol, Triglycerides which will be assessed via pathology
Timepoint [6] 368227 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [7] 368228 0
Changes to kidney health markers (composite secondary outcome) including blood urea, creatinine, eGFR, fibroblast growth factor 23 levels assessed via pathology
Timepoint [7] 368228 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [8] 368229 0
Blood Pressure (composite secondary outcome) assessed by automatic Blood pressure machine.
Timepoint [8] 368229 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [9] 368230 0
Changes to anthropometric measures (composite secondary outcome) which will be assessed by weight, BMI, waist circumference and body composition (Fat mass, FFM) measured using SECA medical Body Composition Analyzer
Timepoint [9] 368230 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [10] 368240 0
Serum phosphate assessed via pathology
Timepoint [10] 368240 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [11] 368243 0
Quality of life scores assessed by the EQ-5D-5L tool
Timepoint [11] 368243 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [12] 368246 0
Symptom burden assessed via the POS- renal tool
Timepoint [12] 368246 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [13] 368247 0
GUT microbiota assessed via stool samples using 16S rRNA sequencing. Collection will be suitable for shot-gun sequencing analysis with further future funding.
Timepoint [13] 368247 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [14] 368248 0
ORAL microbiota assessed via stool samples using 16S rRNA sequencing. Collection will be suitable for shot-gun sequencing analysis with further future funding
Timepoint [14] 368248 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).
Secondary outcome [15] 416872 0
Diet quality and nutritional status (composite secondary outcome) will be assessed using diet histories, 3 day food records, short food frequency questionnaire and 7-point SGA.
Timepoint [15] 416872 0
Assessed baseline (week 1), end of first arm (week 6), end of washout/ second baseline (week 10) and end of second arm (week 16).

Eligibility
Key inclusion criteria
- Participants diagnosed with stage 3-4 CKD non-dialysing/ pre-dialysis (eGFR 15-59mL/min per 1.73m2) or individuals deemed suitable by the medical team (Nephrologist).
- Adults (aged 18 years old or more)
- Participants must be able to give informed consent; i.e. have no major cognitive or sensory impairment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Individuals who are less than 18 years of age
• Individuals with intellectual or mental impairment as well as those with a hearing impairment will only be excluded if they cannot follow safety simple instructions due to concerns relevant to the safety of the patient.
• Individuals receiving dialysis
• Individuals diagnosed with dysphagia and/or require texture modified diet
• Any women who are found to be pregnant during the trial would need to be immediately excluded due to the increased medical demands of a pregnancy in kidney disease.
• Individuals with past or present radiation to the bowel or large bowel resection
• Individuals with advanced colorectal cancer
• Individuals who consumed antibiotic therapy within 1 months of study commencement
• Individuals with medically diagnosed irritable bowel syndrome, crohn’s disease or ulcerative colitis;
• Individuals who have had a clinically significant change to their immunosuppressant dose within the last 6 months (determined by the medical team) of study commencement.

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 will only be known by the external statistician. Allocation will involve contacting the holder of the allocation schedule who is "off-site" or at a central administration site.

The member(s) of the research team who are providing the education/ dietary prescription will not be aware of allocation until consented participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be by computer-generated sequence using random permuted blocks which will be completed by external statistician from the research group.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Crossover
Other design features
Nil
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/05/2019
Actual
20/01/2020
Date of last participant enrolment
Anticipated
Actual
26/04/2021
Date of last data collection
Anticipated
Actual
3/09/2021
Sample size
Target
30
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13356 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 25955 0
2500 - Wollongong

Funding & Sponsors
Funding source category [1] 301658 0
University
Name [1] 301658 0
University of Wollongong
Country [1] 301658 0
Australia
Primary sponsor type
University
Name
University of Wollongong
Address
University of Wollongong
Northfields Avenue
Wollongong, NSW, 2522
Country
Australia
Secondary sponsor category [1] 301437 0
None
Name [1] 301437 0
Address [1] 301437 0
Country [1] 301437 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302378 0
The University of Wollongong and the Illawarra Shoalhaven Local Health District (ISLHD) ethics committee
Ethics committee address [1] 302378 0
Ethics committee country [1] 302378 0
Australia
Date submitted for ethics approval [1] 302378 0
11/03/2019
Approval date [1] 302378 0
16/05/2019
Ethics approval number [1] 302378 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90022 0
Ms Jordan Stanford
Address 90022 0
Building 41
University of Wollongong
Northfields Avenue
Wollongong
NSW, 2522
Country 90022 0
Australia
Phone 90022 0
+61 2 4221 4600
Fax 90022 0
Email 90022 0
[email protected]
Contact person for public queries
Name 90023 0
Anita Stefoska-Needham
Address 90023 0
Building 41
University of Wollongong
Northfields Avenue
Wollongong
NSW, 2522
Country 90023 0
Australia
Phone 90023 0
+61 242 21 4707
Fax 90023 0
Email 90023 0
[email protected]
Contact person for scientific queries
Name 90024 0
Karen Charlton
Address 90024 0
Building 41
University of Wollongong
Northfields Avenue
Wollongong
NSW, 2522
Country 90024 0
Australia
Phone 90024 0
+61 2 4221 4754
Fax 90024 0
Email 90024 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?

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.