Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000127707
Ethics application status
Approved
Date submitted
27/01/2013
Date registered
1/02/2013
Date last updated
11/02/2021
Date data sharing statement initially provided
11/02/2021
Date results information initially provided
11/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Salt and its effects on endothelial function in patients with type two diabetes
Scientific title
Effect of salt supplementation on sympathetic nervous system activity and endothelial function in people with type two diabetes
Secondary ID [1] 281848 0
Nil
Universal Trial Number (UTN)
U1111-1138-9513
Trial acronym
NIl
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 288207 0
Endothelial Function 288208 0
Sympathetic nervous system activity 288209 0
Condition category
Condition code
Metabolic and Endocrine 288576 288576 0 0
Diabetes
Cardiovascular 288623 288623 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 288624 288624 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Salt loading (Slow Sodium, NaCl at a dose of 100mmol/24h in 3 divided doses) or placebo to be taken daily for 3 weeks each. Slow release salt capsules manufactured by Thompson’s compounding pharmacy.
As this is a cross over study, there will be a three week washout period between both treatment arms.
Intervention code [1] 286407 0
Treatment: Other
Comparator / control treatment
Identical placebo tablets will be manufactured by Thompson’s Compounding Pharmacy in Bulleen, Victoria. These will be identical in appearance, taste and size but will not contain any salt (NaCl).
Control group
Placebo

Outcomes
Primary outcome [1] 288730 0
Patients with Type 2 diabetes (Cases) with habitual salt intake in the lowest tertile (<150mmol/24h), have increased baseline Sympathetic Nervous System (SNS) activity and increased endothelial dysfunction compared to Controls.
Timepoint [1] 288730 0
During baseline visit, week three and week nine of the trial, the SNS will be measured by muscle sympathetic Muscle Sympathetic Nerve Activity (MSNA) and by Pulse Amplitude Tonometry (EndoPAT). For endothelial dysfunction, this will be measured at baseline and the start of week three, week six and week nine.
Primary outcome [2] 288731 0
Salt loading (100mmol/24h over 3 weeks) will reduce SNS activity and improve endothelial function in Cases, not Controls.
a.Reduction in SNS activity will be measured by Muscle Sympathetic Nerve Activity (MSNA).
b.Improved endothelial function will be measured by Pulse Amplitude Tonometry (EndoPAT).
c.Improved endothelial function will be measured by endothelial microparticles (EMP).
Timepoint [2] 288731 0
Nine weeks
Secondary outcome [1] 300855 0
NIl
Timepoint [1] 300855 0
NIl

Eligibility
Key inclusion criteria
Blood Pressure <150/80
Body Mass Index matched
2 out of 3 24 hour urine collections <150mmol/24h
35 patients will be recruited into the Type Two Diabetes arm and 35 non-diabetic patients will be recruited into the control arm.
Minimum age
50 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Other active significant medical problems, including clinical autonomic neuropathy

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)
This is a randomised double blind, controlled, cross-over study with the intervention being salt loading (100mmol/24h) versus placebo in patients with T2DM and controls (normotensive but age, sex and BMI matched). The pharmacy department will be responsible for allocating tablets which will be in a non-identified envelope to patient or pharmacy department.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
The statistical power for this study will be based on measurements of endothelial function and SNS. As participants will be their own controls, a sample size of 29 will ensure a power of 90% and a type 1 error to detect an effect on RHI of at least 22% (difference 0.4404) with a standard deviation of 0.5753. Thirty five participants will be recruited to allow for drop outs. A sample size of 21 subjects per treatment arm will have an 80% power to demonstrate a difference in MSNA of 20% or greater (a = 0.05). Hence, allowing for possible procedural failure and participant withdrawal from the study 35 subjects will be recruited. Moreover, treatment effects on MSNA, EndoPAT, EMPs will be analysed using a 2-way ANOVA, one between-group factor being cases versus controls and one within-subject factor being salt supplement versus placebo.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
11/02/2013
Actual
1/08/2013
Date of last participant enrolment
Anticipated
11/12/2013
Actual
31/08/2016
Date of last data collection
Anticipated
Actual
18/11/2019
Sample size
Target
70
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 504 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 6245 0
3081 - Heidelberg West

Funding & Sponsors
Funding source category [1] 286630 0
Hospital
Name [1] 286630 0
Austin Medical Research foundation
Country [1] 286630 0
Australia
Primary sponsor type
Individual
Name
Dr Elif Ilhan Ekinci, Director of Diabetes
Address
Department of Endocrinology, Austin Health
Level 2 Centaur Building, Repatriation Campus Heidelberg West, VIC 3081
Country
Australia
Secondary sponsor category [1] 285415 0
Individual
Name [1] 285415 0
Professor George Jerums
Address [1] 285415 0
Department of Endocrinology, Austin Health. Level 2 Centaur Building, Repatriation Campus Heidelberg West, VIC 3081
Country [1] 285415 0
Australia
Other collaborator category [1] 277269 0
Other Collaborative groups
Name [1] 277269 0
Baker IDI Heart & Diabetes Institute
Address [1] 277269 0
75 Commercial Road
Melbourne, Victoria 3004
Country [1] 277269 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288708 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 288708 0
145 Studley road
Heidelberg, Victoria
3084
Ethics committee country [1] 288708 0
Australia
Date submitted for ethics approval [1] 288708 0
Approval date [1] 288708 0
13/09/2012
Ethics approval number [1] 288708 0
HREC/12/Austin/63

Summary
Brief summary
A high salt diet is associated with an increased risk of hypertension. By contrast, in patients with type 2 diabetes, a low salt diet is associated with an increased risk for cardiovascular and total mortality. As a low salt intake may increase sympathetic nervous system (SNS) activity, we aim to determine baseline SNS activity and endothelial function in patients with diabetes consuming a habitual low salt diet and determine whether salt loading reduces SNS activity and enhances endothelial function.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37370 0
Dr Elif Ilhan Ekinci
Address 37370 0
Department of Endocrinology, Austin Health
Level 2 Centaur Building, Repatriation Campus Heidelberg West, VIC 3081
Country 37370 0
Australia
Phone 37370 0
+61 3 94965000
Fax 37370 0
Email 37370 0
elif.ekinci@austin.org.au
Contact person for public queries
Name 37371 0
Dr Sara Baqar
Address 37371 0
Department of Endocrinology, Austin Health
Level 2 Centaur Building, Repatriation Campus Heidelberg West, VIC 3081
Country 37371 0
Australia
Phone 37371 0
+61 3 94965000
Fax 37371 0
Email 37371 0
sara.baqar@austin.org.au
Contact person for scientific queries
Name 37372 0
Dr Elif Ilhan Ekinci
Address 37372 0
Department of Endocrinology, Austin Health
Level 2 Centaur Building, Repatriation Campus Heidelberg West, VIC 3081
Country 37372 0
Australia
Phone 37372 0
+61 3 94965000
Fax 37372 0
Email 37372 0
elif.ekinci@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All individual participant data after deidentification
When will data be available (start and end dates)?
Immediately following publication. No end date.
Available to whom?
Anyone who wishes to access the data
Available for what types of analyses?
For any purpose
How or where can data be obtained?
Proposals to be sent to sara.baqar@austin.org.au 36 months after publication.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes 25 November 2019 Effect of Salt Supplementation... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffect of salt supplementation on sympathetic activity and endothelial function in salt-sensitive type 2 diabetes.2020https://dx.doi.org/10.1210/clinem/dgz219
N.B. These documents automatically identified may not have been verified by the study sponsor.