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Trial registered on ANZCTR


Registration number
ACTRN12618001958279p
Ethics application status
Submitted, not yet approved
Date submitted
23/11/2018
Date registered
4/12/2018
Date last updated
4/12/2018
Date data sharing statement initially provided
4/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of Mineralocorticoid Receptor Blockade on Metabolism - A Clinical Trial
Scientific title
Defining the Novel Effects of Mineralocorticoid Receptor Antagonism on Metabolism in Humans – A Randomised Controlled Trial

Secondary ID [1] 296698 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 310545 0
Condition category
Condition code
Metabolic and Endocrine 309257 309257 0 0
Metabolic disorders
Diet and Nutrition 309280 309280 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised to either arm 1 (oral spironolactone 100 mg once daily) or arm 2 (oral placebo once daily) for 16 weeks
Double-blinded
Adherence will be assessed by pill counting of returned medication bottles
Intervention code [1] 313011 0
Treatment: Drugs
Comparator / control treatment
Placebo-controlled (microcellulose)
Control group
Placebo

Outcomes
Primary outcome [1] 308236 0
Change in total fat mass on dual energy X-ray absorptiometry (DEXA) scan

Timepoint [1] 308236 0
at 16 weeks post-treatment
Primary outcome [2] 308237 0
Change in insulin sensitivity assessed by hyperinsulinaemic-euglycaemic clamp
Timepoint [2] 308237 0
at 16 weeks post-treatment
Secondary outcome [1] 354349 0
Change in brown adipose tissue activity assessed by 18F-Fluorodeoxy-glucose Positron-emission-tomography-CT (FDG-PET-CT)
Timepoint [1] 354349 0
at 8 weeks post-treatment
Secondary outcome [2] 354350 0
Changes in the expression of genes involved in metabolism and inflammation in abdominal subcutaneous adipose tissue biopsies (exploratory)
Timepoint [2] 354350 0
at 8 weeks post-treatment
Secondary outcome [3] 354351 0
Change in Body weight measured using digital scale

Timepoint [3] 354351 0
at 16 weeks post-treatment
Secondary outcome [4] 354352 0
Change in fasting lipids on blood test (exploratory)
Timepoint [4] 354352 0
at 16 weeks post-treatment
Secondary outcome [5] 354353 0
Change in visceral fat mass on DEXA
Timepoint [5] 354353 0
at 16 weeks post-treatment
Secondary outcome [6] 354354 0
Change in metabolic and substrate oxidation rates assessed by indirect calorimetry (composite)
Timepoint [6] 354354 0
at 16 weeks post-treatment

Eligibility
Key inclusion criteria
BMI 25-40 kg/m2
Minimum age
18 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
(i) estimated glomerular filtration rate (eGFR) less than 60 ml/min
(ii) serum potassium more than 5mmol/L in a non-haemolysed blood sample
(iii) thyroid or endocrine dysfunction
(iv) significant organ dysfunction such as heart failure, liver failure
(v) active malignancy
(vi) pregnant or planning pregnancy
(vii) unable to provide informed consent
(viii) alcohol intake >14 standard drinks per week or smoking
(ix) Unable to maintain stable diet and lifestyle during the study period
(x) taking medications that may interact with spironolactone or have effect on metabolism such as anti-hypertensives acting on the renin-angiotensin or sympathetic system, diuretics, anti-diabetic medications, corticosteroids, anti-psychotics

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified randomisation according to the BMI (25-30 or >30 kg/m2) in 1:1 ratio
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size of 32 is estimated to detect a significant (P < 0.05, 2-sided) difference in fat mass of 1 ± 0.9kg (mean ± standard deviation) and insulin sensitivity of 20 ± 18% between the placebo and spironolactone arms with 80% power, assuming a drop-out rate of 20%.

The differences in outcomes from baseline after spironolactone vs that after placebo will be compared using 2-tailed t-test or ANOVA as appropriate.

Recruitment
Recruitment status
Not yet 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] 12538 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 24919 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 301278 0
Self funded/Unfunded
Name [1] 301278 0
N/A
Address [1] 301278 0
N/A
Country [1] 301278 0
Primary sponsor type
Individual
Name
Dr Moe Thuzar
Address
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
Brisbane, Queensland 4102, Australia
Country
Australia
Secondary sponsor category [1] 300925 0
Individual
Name [1] 300925 0
Professor Michael Stowasser
Address [1] 300925 0
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
Brisbane, Queensland 4102, Australia
Country [1] 300925 0
Australia
Secondary sponsor category [2] 300928 0
Hospital
Name [2] 300928 0
Princess Alexandra Hospital Metro South Health
Address [2] 300928 0
199 Ipswich Road, Woolloongabba
Brisbane, Queensland 4102, Australia
Country [2] 300928 0
Australia
Secondary sponsor category [3] 300929 0
Hospital
Name [3] 300929 0
University of Queensland
Address [3] 300929 0
Translational Research Institute
37 Kent Street, Woolloongabba
Brisbane, Queensland 4102, Australia
Country [3] 300929 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302022 0
Metro South Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 302022 0
Centres for Health Research
Level 7 Translational Research Institute Building
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Ethics committee country [1] 302022 0
Australia
Date submitted for ethics approval [1] 302022 0
14/11/2018
Approval date [1] 302022 0
Ethics approval number [1] 302022 0

Summary
Brief summary
Obesity and related cardiometabolic diseases represents an escalating global health challenge, requiring new therapeutic targets. Mineralocorticoid receptors (MRs) are hormone receptors present on fat cells, in high abundance in obese subjects. In animals, blocking the MRs by a tablet called spironolactone protects against obesity and diabetes over time. This project will investigate whether spironolactone provides long-term metabolic benefits in humans.
Thirty-two young overweight/obese subjects will be recruited. Half will be randomly assigned to a 16-week treatment with spironolactone and the other half to placebo (medication-free tablet). Assessments including body-composition scan, nuclear imaging using a glucose tracer, calorimetry, blood tests, abdominal fat sampling will be undertaken before and after treatment to determine whether spironolactone improves body fat mass, tissues glucose uptake and function of fat cells. The results will help determine the novel therapeutic potential of MR blockade for management of obesity and metabolic diseases
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88866 0
Dr Moe Thuzar
Address 88866 0
Department of Endocrinology & Diabetes
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
Brisbane, Qld 4102
Country 88866 0
Australia
Phone 88866 0
+61 7 3176 2111
Fax 88866 0
Email 88866 0
m.thuzar@uq.edu.au
Contact person for public queries
Name 88867 0
Dr Moe Thuzar
Address 88867 0
Department of Endocrinology & Diabetes
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
Brisbane, Qld 4102
Country 88867 0
Australia
Phone 88867 0
+61 7 3176 2111
Fax 88867 0
Email 88867 0
m.thuzar@uq.edu.au
Contact person for scientific queries
Name 88868 0
Dr Moe Thuzar
Address 88868 0
Department of Endocrinology & Diabetes
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba
Brisbane, Qld 4102
Country 88868 0
Australia
Phone 88868 0
+61 7 3176 2111
Fax 88868 0
Email 88868 0
m.thuzar@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only group data will be reported
What supporting documents are/will be available?
No other documents available
Summary results
No Results