None listed
Conditions
Brief summary
Metabolic syndrome and cardiovascular diseases (CVDs) represent the major cause of morbidity and mortality globally. According to the World Health Organisation, more people die annually from CVDs than from any other cause. Hormones underpin the pathophysiological changes surrounding the disease progression. Steroids such as prednisolone are one of the most widely prescribed and effective therapeutics for a variety of inflammatory and autoimmune conditions including inflammatory arthritis, arteritis, asthma, sarcoidosis and nephritis due to their powerful anti-inflammatory effects, but benefits are limited by serious cardiometabolic adverse effects. To date, there is no established specific means to counteract the cardiometabolic complications. There is strong evidence in animals that the adverse cardiometabolic effects of steroids are mediated by closely-related hormone receptors called mineralocorticoid receptors (MRs) which are present on fat cells, heart and immune cells, and that blockade of MRs (MR antagonism) protects against steroid-induced cardiometabolic complications while maintaining the anti-inflammatory benefit. This body of work will define, for the first time in humans, the therapeutic potential of MR antagonism to counteract steroid-induced adverse metabolic and cardiac complications, and provide novel evidence for paradigm shifts in the management of patients exposed to excess steroids.
Interventions
Arm 1 - oral spironolactone capsule 100mg daily for 12 weeks in a double-blind RCT followed by an open label phase comprising treatment with oral spironolactone capsule 100mg daily x another 12 weeks
Sponsors
Dr Moe Thuzar
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(i) female (ii) age at least 18 years (iii) requiring glucocorticoids (GC) therapy (equivalent to at least 7.5mg/day of prednisolone average) for at least the next 3 months (iv) on nil or stable other systemic immunomodulatory drugs
Exclusion criteria
any of the following - (i) upright systolic blood pressure <100 mmHg (ii) estimated glomerular filtration rate (eGFR) less than 60 ml/min (iii) serum potassium more than 5mmol/L in a non-haemolysed blood sample (iv) thyroid or endocrine dysfunction, other than diabetes (v) significant organ dysfunction such as heart failure, liver failure (vi) moderate-severe valvular or unstable ischaemic heart disease or rhythm disturbances (vii) active malignancy (viii) transplant recipient (ix) undertaking a weight loss regimen or history of previous bariatric surgery (x) pregnant or planning pregnancy, or not willing to use effective birth control measures throughout the study period while sexually active in a heterosexual relationship and of reproductive age (xi) unable to provide informed consent
Outcome results
None listed