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Trial registered on ANZCTR


Registration number
ACTRN12623001237673
Ethics application status
Approved
Date submitted
14/07/2023
Date registered
30/11/2023
Date last updated
30/11/2023
Date data sharing statement initially provided
30/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of extra-renal effects of SGLT2-inhibitors in anuric haemodialysis patients using microneurography
Scientific title
Assessment of the effect of Empagliflozin on sympathetic tone and extra-renal effects in anuric haemodialysis patients using microneurography
Secondary ID [1] 310092 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
End Stage Kidney Disease (ESKD) with Anuria 330644 0
Condition category
Condition code
Renal and Urogenital 327467 327467 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Effects of Empagliflozin on Sympathetic Nervous System; assessed using microneurography

- the dose administered, 25mg once daily in the morning,
- the duration of administration, 6 weeks, then stop
- the mode of administration, oral tablet,
- Strategies used to monitor adherence to the intervention: smart phone reminder, pill counting, and reminder on dialysis sessions,
Intervention code [1] 326492 0
Treatment: Drugs
Comparator / control treatment
No control group. Effect of the medication will be compared pre vs post exposure.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335333 0
Difference in sympathetic tone before and after initiation of Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors measured at weeks 0, 3, and 6. Difference in sympathetic tone is measured using a tungsten microelectrode inserted in a muscle fascicle of the peroneal nerve at the fibular head.
Timepoint [1] 335333 0
Week 0 (baseline), weeks 3 and 6 (primary endpoint) post-commencement of intervention,
Secondary outcome [1] 423987 0
•Variability in sympathetic response to acute stressors (mental stress, cold pressor, and hand grip tests) as measured by microneurography (as a composite secondary outcome)
Timepoint [1] 423987 0
Week 0 (baseline), weeks 3 and 6 post-commencement of intervention,
Secondary outcome [2] 428114 0
•Differences in sympathetic tone changes through the study between diabetic vs non-diabetic participants enrolled using microneurographic recordings of peroneal nerve
Timepoint [2] 428114 0
Week 0 (baseline), weeks 3 and 6 post-commencement of intervention,
Secondary outcome [3] 428115 0
•Change in blood pressure throughout the study using digital blood pressure machine
Timepoint [3] 428115 0
Week 0 (baseline), weeks 3 and 6 post-commencement of intervention,
Secondary outcome [4] 428116 0
•Changes in glycaemic parameters throughout the study, using plasma glucose levels and capillary blood glucose levels
Timepoint [4] 428116 0
Week 0 (baseline), weeks 3 and 6 post-commencement of intervention,
Secondary outcome [5] 428117 0
•Changes in Brain Natriuretic Peptide (BNP) plasma levels throughout the study
Timepoint [5] 428117 0
Week 0 (baseline), weeks 3 and 6 post-commencement of intervention,
Secondary outcome [6] 428118 0
•Changes in central blood pressure variability throughout the study assessed using digital blood pressure machine
Timepoint [6] 428118 0
Week 0 (baseline), weeks 3 and 6 post-commencement of intervention,
Secondary outcome [7] 428501 0
•Changes in heart rate variability throughout the study assessed using a pulse oximetry
Timepoint [7] 428501 0
Week 0 (baseline), weeks 3 and 6 post-commencement of intervention,
Secondary outcome [8] 428502 0
•Changes in postural blood pressure variability throughout the study assessed using digital blood pressure machine
Timepoint [8] 428502 0
Week 0 (baseline), weeks 3 and 6 post-commencement of intervention,

Eligibility
Key inclusion criteria
• Adults 18 years and older
• Anuric haemodialysis patients
• Able to mobilise independently
• BP <160/90 mmHg
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients with Type 1 Diabetes
• Patients on SGLT2-inhbitors prior to the study will be excluded.
• History of Unilateral or Bilateral Nephrectomy, chronic liver disease, heart failure [New York Heart Association (NYHA) class II-IV}, or secondary hypertension
• Pregnancy (females of childbearing potential must have negative pregnancy test)
• Relative or absolute contraindication to empagliflozin, including active urinary or genital tract infection, or known drug allergy
• Severe peripheral vascular disease or neuropathy
• Initiation of alpha-blockers, beta-blockers or moxonidine within the preceding 6 weeks
• Cardiovascular event(s) within the last 6 months
• Unstable psychiatric condition or inability to understand and attend appointments
• On medications such as corticosteroids, multiple antidepressants, and antipsychotics

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
continuous variables are expressed as mean ± standard deviation (SD) for normally distributed data or as median [interquartile range (IQR)] for non-normally distributed data, and as proportions for categorical variables.

Assessment of the difference in the value pre and post intervention will be assessed by paired T test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2023
Actual
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
13/03/2024
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 25096 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 40766 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 314254 0
Hospital
Name [1] 314254 0
Royal Perth Hospital
Country [1] 314254 0
Australia
Primary sponsor type
Other
Name
Dobney Hypertension Centre
Address
Royal Perth Hospital - Medical research Foundation, 50 Murray St, Perth WA 6000
Country
Australia
Secondary sponsor category [1] 316191 0
None
Name [1] 316191 0
Address [1] 316191 0
Country [1] 316191 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313374 0
Royal Perth Hospital-Human Research Ethics Committee
Ethics committee address [1] 313374 0
Royal Perth Hospital, Victoria Square, Perth, WA, 6000
Ethics committee country [1] 313374 0
Australia
Date submitted for ethics approval [1] 313374 0
01/09/2022
Approval date [1] 313374 0
15/02/2023
Ethics approval number [1] 313374 0
RGS0000003840

Summary
Brief summary
Sodium Glucose Co-transporter 2 inhibitors (SGLT2i) have been shown to reduce cardiovascular morbidity, mortality and have reno-protective effects. Though their glycosuric effects remain the most studied mechanism, multiple other mechanisms of action have been theorized. This includes extra-renal effects on organs such as the brain, heart, and the sympathetic nervous system (SNS).

Increased sympathetic tone is a key feature in various conditions such as chronic kidney disease, type 2 diabetes mellitus, obesity, metabolic syndrome, and heart failure. Limiting the renal effects of SGLT2i by administering them to patients who do not produce urine will allow more accurate assessment of their extra-renal impacts and effectiveness in reducing sympathetic nerve activity.

This investigator-led, open-label, prospective, mechanistic study aims to investigate the extra-renal effects of SGLT2i on the SNS, by administering empagliflozin to anuric haemodialysis patients and measuring SNS activity using microneurography of the popliteal nerve, over 6 weeks. We hypothesize that the use of empagliflozin will result in reduced sympathetic drive, which in turn would add mechanistic proof to the extra-renal benefits of SGLT2i.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127922 0
Dr Awf Abdulrahman Shaban
Address 127922 0
Nephrology Department, Royal Perth Hospital, Victoria Square, Perth WA 6000
Country 127922 0
Australia
Phone 127922 0
+61455332490
Fax 127922 0
Email 127922 0
awfalsham@yahoo.com
Contact person for public queries
Name 127923 0
Dr Awf Abdulrahman Shaban
Address 127923 0
Nephrology Department, Royal Perth Hospital, Victoria Square, Perth WA 6000
Country 127923 0
Australia
Phone 127923 0
+61892242244
Fax 127923 0
Email 127923 0
awfalsham@yahoo.com
Contact person for scientific queries
Name 127924 0
Dr Awf Abdulrahman Shaban
Address 127924 0
Nephrology Department, Royal Perth Hospital, Victoria Square, Perth WA 6000
Country 127924 0
Australia
Phone 127924 0
+61455332490
Fax 127924 0
Email 127924 0
awfalsham@yahoo.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
not available yet


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19650Study protocol    386216-(Uploaded-11-07-2023-03-54-27)-Study-related document.docx
19651Ethical approval    386216-(Uploaded-11-07-2023-03-55-16)-Study-related document.pdf
19652Informed consent form    386216-(Uploaded-20-10-2023-18-26-37)-Study-related document.docx



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.