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Trial registered on ANZCTR


Registration number
ACTRN12611001097932
Ethics application status
Approved
Date submitted
17/10/2011
Date registered
21/10/2011
Date last updated
1/02/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of lowering salt intake on ambulatory blood pressure and cardiovascular risk in patients with chronic kidney disease
Scientific title
A double-blind placebo-controlled trial of low versus moderate sodium intake to reduce ambulatory blood pressure and cardiovascular risk in patients with moderate chronic kidney disease
Secondary ID [1] 273206 0
Nil
Universal Trial Number (UTN)
U1111-1125-2149
Trial acronym
LowSALT CKD Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Kidney Disease 278972 0
Cardiovascular risk factors 278988 0
Condition category
Condition code
Renal and Urogenital 279148 279148 0 0
Kidney disease
Cardiovascular 279170 279170 0 0
Hypertension
Diet and Nutrition 279171 279171 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a 2 phase study with phase 1 encompassing a randomised, controlled, double-blinded cross-over trial, and phase 2 involving long-term follow up to six months.

Trial periods:

Phase 1:
1) Run-in (washout) period: 1 week.
All participants will begin the trial consuming a low sodium diet (containing less than 60 mmol sodium per day).

2) First intervention period: 2 week.
All participants will continue on a low sodium diet but will be randomised to receive either sodium capsules (120 mmol of sodium chloride per day, resulting in a total target intake of 180 mmol per day) or placebo capsules (sodium consumed via diet only resulting in a total sodium intake of 60 mmol per day).

3) Washout period: 1 week.
Participants will continue on a low sodium diet as per 1) above

4) Second intervention period: 2 week.
Participants will crossover to the other tablets as per 2) above.

The order of the two interventions (low sodium intake; moderate sodium intake) will be randomised. Neither the participants nor the investigators will be aware of the treatment order.

Sodium restriction to 60 mmol per day will be facilitated by dietary education from the study dietitians with the aim to replace sodium-rich foods with lower sodium alternatives, and partial provision of food including pre-prepared meals, snack foods, spreads and sauces. Participants will have minimum fortnightly contact with the study dietitians (approximately 1 hour) to verify their dietary history forms and provide dietary education.

Phase 2: 20 weeks
Phase 2 will not include a control group; All phase 1 participants will continue on a low salt diet (goal < 100 mmol / day) to assess the translation of phase 1 results
into a practical setting and to examine long-term adherence to a low salt diet.

Sodium restriction to < 100 mmol per day will be facilitated by continued dietary education from the study dietitians by minimum monthly phone calls. Follow up measurements will occur at 4 months and 6 months (from baseline)
Intervention code [1] 269542 0
Prevention
Intervention code [2] 269543 0
Lifestyle
Comparator / control treatment
Moderate sodium intake (60 mmol dietary intake plus 120 mmol from sodium chloride capsules)
Control group
Active

Outcomes
Primary outcome [1] 279792 0
Change in 24hr Ambulatory Blood Pressure (mm hg) assessed using ambulatory blood pressure monitor (TM-2430 Ambulatory Blood Pressure Monitor, A & D Medical, Australia).
Timepoint [1] 279792 0
Ambulatory blood pressure will be measured at baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8). Measurements will be taken over 24 hours every 20 minutes from 6am to 10pm and every 30 minutes from 10pm to 6am.
Secondary outcome [1] 294437 0
Arterial Stiffness assessed via carotid-femoral pulse wave velocity (PWV) and radial pulse wave analysis using the SphygmoCor CPV System (AtCor Medical, Australia).
Timepoint [1] 294437 0
Baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).
Secondary outcome [2] 294465 0
Markers of renal damage: 24-hr urinary protein and albumin (via 24-hr urine sample), and estimated glomerular filtration rate (via serum creatinine)
Timepoint [2] 294465 0
Baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).
Secondary outcome [3] 294466 0
Fluid status assessed using multi-frequency bio-impedance spectroscopy using Body Composition Monitor (Fresenius Medical Care, Germany), urine output (via 24 hour urine sample), weight and N-Terminal Pro-Brain Natriuretic Peptide (via blood sample), and thirst via Xerostomia Index.
Timepoint [3] 294466 0
Baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).
Secondary outcome [4] 294467 0
Markers of inflammation, such as C-RP and adipokines, via blood sample
Timepoint [4] 294467 0
Baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).
Secondary outcome [5] 294468 0
Stimulation of renin-angiotensin-aldosterone system measured via blood sample using routine methods
Timepoint [5] 294468 0
Baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).
Secondary outcome [6] 294469 0
Daytime sleepiness, as a marker of sleep apnea, measured via Epworth Sleepiness Scale
Timepoint [6] 294469 0
Baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).
Secondary outcome [7] 294490 0
Taste acuity, measured via acute taste-test study.

Taste identification testing will be performed in accordance with the International Standards Organisation (ISO), ISO 3972:1991-Sensory analysis- Methodology-Method of investigating sensitivity of taste (International Organisation for Standardisation, 1991). Participants will be presented with solutions which represent each of the five basic taste qualities, and will be asked to identify the taste and rate it according to intensity on a visual analogue scale
Timepoint [7] 294490 0
Baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).
Secondary outcome [8] 294491 0
Barriers and enablers to adherence measured via beliefs about dietary compliance scale (from (Welch, Bennett et al. 2006)) and attitudes to dietary recommendations (modified from (Brekke, Sunesson et al. 2004).
Timepoint [8] 294491 0
Baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).
Secondary outcome [9] 294500 0
Dietary intake and adherence measured using multiple methods including:
- 24 hour urine samples (sodium and potassium),
- semi-quantitative dietary history forms (verified by study dietitians),
- a daily checklist where the participant records intake of study medication and high-sodium foods (to assess daily variation), and
- mid-stream urine samples (sodium and potassium)
Timepoint [9] 294500 0
24 hour urine and dietary histories at baseline (Visit 0), at the end of each of the two 2 week interventions (Visit 3 and 6), and at 4 months and 6 months (Visit 7 and 8).

Daily checklist and mid-stream urine samples will be collected weekly throught phase 1 (visit 1-6) and both phase 2 follow ups (Visits 7-8).

Eligibility
Key inclusion criteria
- CKD stage 3 or 4 (GFR 15-59 ml/min/1.73m2) patients under the care of a nephrologist at the Princess Alexandra Hospital
- Aged at least 18 years
- Able to provide informed consent
- Systolic BP 130-169 mmHg
- Diastolic BP >70 mmHg.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Unable or unwilling to attend the PAH for visits as specified by the study protocol
- Receiving renal replacement therapy (dialysis or transplant) or likely to within the trial duration
- Salt-wasting CKD (as diagnosed by nephrologist)
- Prescribed > 1680 mg of sodium bicarbonate and not able to cease this medication for six weeks
- Pregnant or breastfeeding
- Life expectancy less than 6 months.
- Current involvement in other intervention
- Unable to comprehend study protocol

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)
Patients have been/will be recruited through the outpatient renal department at the Princess Alexandra Hospital.

Following 1 week run-in period, participants will be consecutively assigned a randomisation number, at the beginning of intervention 1 participants will be provided with the study medication labelled with their study number. Neither the participants nor the investigators will know which medication will be provided at each intervention.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule was created using a computerised sequence generation in a 1:1 ratio by a statistician who is not part of the research team and sent directly to the pharmacy dispensing the medications.
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 1
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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] 7417 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 15220 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 270039 0
Charities/Societies/Foundations
Name [1] 270039 0
Princess Alexandra Hospital Private Practice Trust Fund
Address [1] 270039 0
Private Practice Unit, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, QLD 4102
Country [1] 270039 0
Australia
Funding source category [2] 270040 0
Charities/Societies/Foundations
Name [2] 270040 0
Kidney Health Australia
Address [2] 270040 0
GPO Box 9993, Melbourne VIC 3001 (National Office)
Country [2] 270040 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital
Address
Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, QLD 4102
Country
Australia
Secondary sponsor category [1] 269011 0
Individual
Name [1] 269011 0
Dr Katrina Campbell
Address [1] 269011 0
Nutrition and Dietetics Department, Ground Floor, Building 15, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, QLD 4102
Country [1] 269011 0
Australia
Other collaborator category [1] 252298 0
Individual
Name [1] 252298 0
Miss Emma Hall
Address [1] 252298 0
Nutrition and Dietetics Department, Ground Floor, Building 15, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, QLD 4102
Country [1] 252298 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271992 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 271992 0
199 Ipswich Road, Woolloongabba, QLD 4102
Ethics committee country [1] 271992 0
Australia
Date submitted for ethics approval [1] 271992 0
14/04/2011
Approval date [1] 271992 0
22/07/2011
Ethics approval number [1] 271992 0
HREC/11/QPAH/235
Ethics committee name [2] 272002 0
University of Queensland Human Research Ethics Committee
Ethics committee address [2] 272002 0
Research and Innovation Division
Cumbrae-Stewart (Building 72)
The University of Queensland
Brisbane, 4072
AUSTRALIA
Ethics committee country [2] 272002 0
Australia
Date submitted for ethics approval [2] 272002 0
26/08/2011
Approval date [2] 272002 0
14/09/2011
Ethics approval number [2] 272002 0
2011000956

Summary
Brief summary
Cardiovascular disease (CVD) is the leading cause of mortality in the chronic kidney disease (CKD) population, and is independently associated with kidney function decline. Dietary sodium intake has been implicated in several traditional and novel risk factors driving both CVD and CKD progression. Despite evidence implicating dietary sodium in the pathogenesis of CVD in CKD, sodium intake in CKD patients remains high and evidence suggests that sodium restriction is not adequately emphasized for CKD patients. Part of the reason for this may be high-quality intervention trials of sodium restriction in CKD patients are lacking. Most evidence has been extrapolated from studies in non-CKD populations. However, as sodium handling is influenced by kidney function; it is highly likely that the CKD population is more susceptible to adverse effects of high dietary sodium. The aim of this study is to examine the effect of reducing sodium intake on blood pressure, progression of renal failure and other cardiovascular risk factors in patients with moderate CKD.
Trial website
Trial related presentations / publications
The effect of lowering salt intake on ambulatory blood pressure to reduce cardiovascular risk in chronic kidney disease (LowSALT CKD study): protocol of a randomized trial
http://www.biomedcentral.com/1471-2369/13/137

McMahon, E. J., et al. (2013). "A Randomized Trial of Dietary Sodium Restriction in CKD." J Am Soc Nephrol. http://www.ncbi.nlm.nih.gov/pubmed/24204003

Campbell, K. L., et al. (2014). "A randomized trial of sodium-restriction on kidney function, fluid volume and adipokines in CKD patients." BMC Nephrol 15: 57. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994521/

McMahon EJ, Bauer J, Hawley CM, Isbel N, Stowasser M, Johnson DW, Hale R & Campbell KL.The effect of lowering salt intake on ambulatory blood pressure to reduce cardiovascular risk in chronic kidney disease (LowSALT CKD study). World Congress of Nephrology. Hong Kong May 31st-June 4th, 2013.

McMahon EJ, Bauer J, Hawley CM, Isbel N, Stowasser M, Johnson DW & Campbell KL. Effect on dietary sodium restriction on blood pressure, proteinuria and fluid volume in chronic kidney disease patients: results of randomised crossover trial and 6-month follow up. Australian and New Zealand Society Of Nephrology Conference 2013. Brisbane September 9th -11th, 2013.
Public notes

Contacts
Principal investigator
Name 33267 0
Dr Katrina Campbell
Address 33267 0
Ipswich Road
Princess Alexandra Hospital, Brisbane
Woolloongabba QLD 4102
Country 33267 0
Australia
Phone 33267 0
+617 3176 7938
Fax 33267 0
Email 33267 0
Katrina_Campbell@health.qld.gov.au
Contact person for public queries
Name 16514 0
Dr Emma Hall
Address 16514 0
Nutrition and Dietetics Department, Ground Floor, Building 15, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, QLD 4102
Country 16514 0
Australia
Phone 16514 0
+617 3176 7938
Fax 16514 0
+617 3176 5619
Email 16514 0
e.hall5@uq.edu.au
Contact person for scientific queries
Name 7442 0
Miss Emma Hall
Address 7442 0
Nutrition and Dietetics Department, Ground Floor, Building 15, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, QLD 4102
Country 7442 0
Australia
Phone 7442 0
+617 3176 7938
Fax 7442 0
+617 3176 5619
Email 7442 0
e.hall5@uq.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary