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Trial registered on ANZCTR


Registration number
ACTRN12613000493741
Ethics application status
Approved
Date submitted
29/04/2013
Date registered
2/05/2013
Date last updated
31/01/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Investigating the effect of synbiotics on uremic toxin concentrations in the pre-dialysis population.
Scientific title
Randomized, double-blind, placebo-controlled crossover study in the pre-dialysis population assessing the benefit of synbiotics on serum uremic toxin concentrations
Secondary ID [1] 282410 0
Nil
Universal Trial Number (UTN)
U1111-1142-4363
Trial acronym
SYNERGY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Kidney Disease 288992 0
Condition category
Condition code
Renal and Urogenital 289333 289333 0 0
Kidney disease
Diet and Nutrition 289334 289334 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will involve 4 stages:
1. Pre-study period (2 weeks)
2. Study period 1 (intervention 1) (6 weeks)
3. “Washout” period (4 weeks)
4. Study period 2 (intervention 2) (6 weeks)
In the pre-study period patients will have measurements taken and discuss with the dietitian about healthy eating for kidney disease. During the study period 1 (intervention 1) the patient will be provided with either placebo powder and tablets (these are designed to have no physical effect) or prebiotic powder and probiotic tablets to take for six weeks. During intervention 2, patients will crossover to the other powder and tablets (ie: if they received placebo in the first six weeks, they will receive the prebiotic powder and probiotic tablets in the second six weeks and vice versa).

Probiotic dose= 40billion CFU 2 x daily
Prebiotic dose= 7.5g 2 x daily

Adherence to the supplements will be monitored through a supplement count and weighing, and adherence to a stable diet will be monitored using 24hr food recalls
Intervention code [1] 287042 0
Treatment: Drugs
Comparator / control treatment
Placebo (capsule- cellulose and powder- maltodextrin)
Control group
Placebo

Outcomes
Primary outcome [1] 289447 0
Free and protein-bound concentrations of serum- indoxyl sulphate and p-cresyl sulphate
Timepoint [1] 289447 0
Baseline, mid point (3 weeks) and end of intervention (6 weeks) for each arm
Secondary outcome [1] 302493 0
Inflammation (serum- CRP, IFN-gamma, TNF-alpha, IL-6) and Oxidative stress (plasma- GPX, MDA and 8-Isoprostanes)
Timepoint [1] 302493 0
Baseline, mid point (3 weeks) and end of intervention (6 weeks) for each arm
Secondary outcome [2] 302494 0
Renal tubule damage & CKD progression
Urinary Kidney Injury Molecule1 (KIM1) and slope of reciprocal serum concentration of creatinine and creatinine clearance (24hr urine collection) vs. time plot, proteinuria and eGFR-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula.
Timepoint [2] 302494 0
Baseline, mid point (3 weeks) and end of intervention (6 weeks) for each arm
Secondary outcome [3] 302495 0
Gut microbiota (fecal sample- next generation sequencing)
Timepoint [3] 302495 0
Baseline and end of intervention (6 weeks) for each arm
Secondary outcome [4] 302496 0
Endotoxemia- (plasma lipopolysaccharides)
Timepoint [4] 302496 0
Baseline, mid point (3 weeks) and end of intervention (6 weeks) for each arm
Secondary outcome [5] 302497 0
Quality of Life (KDQOL)
Timepoint [5] 302497 0
End of intervention (6 weeks) (for each arm)
Secondary outcome [6] 302498 0
Dietary compliance- diet history interviews and 24hr recalls
Timepoint [6] 302498 0
Baseline, mid point (3 weeks) and end of intervention (6 weeks) for each arm

Eligibility
Key inclusion criteria
*CKD stage IV: GFR stable between 10-30 ml/min/1.73m2 (for the past 3 months)
*Able to provide informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Previous transplant or on immunosuppressants
*Receiving/ or have received radiation to the bowel
*Received prebiotic, probiotic or anti-biotic therapy within 1 month of study commencement
*Non-English speaking
*Unable/unwilling to comply with frequent follow-up
*Active medically diagnosed Irritable Bowel Syndrome
*Life expectancy limited due to pre-existing malignancy or other disease (<6 months)
*Likely to progress to dialysis within 6 months as determined by the treating physician
*Likely transplant recipient within 6 months
*Pregnancy
*Severely malnourished (Subjective Global Assessment: C)

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)
Informed written consent will be obtained upon recruitment of all participants. The participant will be informed of the purpose, their involvement, and any potential risk or benefits surrounding their involvement in the study. The participant will be provided with written information that they can discuss with their family or doctor before consenting. The participants will be informed that they can withdraw at any time.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An external statistical consultant will undertake the
computer-generated randomization for the order of the
intervention in blocks, blinded to the investigators
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
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
With 1:1 recruiting, we will require 26 patients to be recruited and to complete both arms. Accounting for 20% dropout, dialysis commencement or mortality (adjustment factor 1.56), 40 patients will be recruited. This sample size is based on an alpha of 5% and power of 80%.
The data will be analysed in accordance with intention-to-treat analysis, using Stata Statistical Software v12. The results will be presented as difference in change (95% CI) between the treatments at the end of each 6 week intervention (controlled for baseline level).

Recruitment
Recruitment status
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)
QLD
Recruitment hospital [1] 956 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 6806 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 287181 0
Charities/Societies/Foundations
Name [1] 287181 0
PA Research Support Scheme (PA Research Foundation)
Address [1] 287181 0
199 Ipswich Rd Woolloongabba, Queensland, 4102
Country [1] 287181 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital
Address
199 Ipswich Rd Woolloongabba, Queensland, 4102
Country
Australia
Secondary sponsor category [1] 285945 0
None
Name [1] 285945 0
Address [1] 285945 0
Country [1] 285945 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289177 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 289177 0
199 Ipswich Rd Woolloongabba, Queensland, 4102
Ethics committee country [1] 289177 0
Australia
Date submitted for ethics approval [1] 289177 0
25/01/2013
Approval date [1] 289177 0
21/02/2013
Ethics approval number [1] 289177 0
HREC/13/QPAH/029

Summary
Brief summary
The main objective of this study is to assess the effect of synbiotics (co-administration of both pre- and probiotics) as a potential treatment targeting damaging kidney toxins related to heart disease and kidney disease progression in advanced chronic kidney disease patients.
Trial website
Trial related presentations / publications
Rossi M, Klein K, Johnson DW, Campbell KL. Pre-, pro-, and synbiotics: do they have a role in reducing uremic toxins? A systematic review and meta-analysis. Int J Nephrol. 2012;2012:673631.
Public notes

Contacts
Principal investigator
Name 39622 0
Dr Katrina Campbell
Address 39622 0
Princess Alexandra Hospital
199 Ipswich Rd Woolloongabba, Queensland, 4102
Country 39622 0
Australia
Phone 39622 0
+61 7 3176 5252
Fax 39622 0
Email 39622 0
katrina_campbell@health.qld.gov.au
Contact person for public queries
Name 39623 0
Ms Megan Rossi
Address 39623 0
Princess Alexandra Hospital
199 Ipswich Rd Woolloongabba, Queensland, 4102
Country 39623 0
Australia
Phone 39623 0
+61 7 3176 5080
Fax 39623 0
Email 39623 0
megan_rossi@msn.com
Contact person for scientific queries
Name 39624 0
Ms Megan Rossi
Address 39624 0
Princess Alexandra Hospital
199 Ipswich Road Woolloongabba, Queensland, 4102
Country 39624 0
Australia
Phone 39624 0
+61 7 3176 5080
Fax 39624 0
Email 39624 0
megan_rossi@msn.com

No information has been provided regarding IPD availability
Summary results
No Results