None listed
Conditions
Brief summary
In 30% of patients with angina, angiography does not reveal obstructive coronary artery disease and the myocardial ischaemia may arise from large vessel coronary artery spasm (vasospastic angina) or coronary microvascular dysfunction (microvascular angina). Collectively, these patients are labelled as ANOCA (Angina with Non Obstructive Coronary Arteries) with 1,800 patients/year being afflicted within South Australia. These patients are significantly disabled with an impaired quality of life and have limited available effective therapies, except for calcium channel blockers in vasospastic angina. There is a need to develop novel therapies that effectively target coronary vasomotor dysfunction. Zinc (Zn), an essential micronutrient, is critical to the functioning of many metalloenzymes and transcription factors. Deficiency of Zn can exacerbate or complicate disease in multiple organ systems. We have demonstrated the importance of Zn homeostasis for the vasculature, including potentiating vasodilator responses via the nitric oxide production and inhibiting endothelin-1-induced constriction. We have recently conducted the first systematic study in Australian cardiac patients, showing a high prevalence of Zn deficiency (29%, n = 400), associated with worse disease. This study is a randomised, double-blind, placebo-controlled crossover study assessing the anti-anginal benefits and impact on health status of Zn 30mg once daily in ANOCA patients experiencing angina at least 3 times/week.
Interventions
Zinc Tablets - Nature's Own Australia
- Dose - 30mg once daily
- Duration - 8 weeks (4 weeks drug intervention and 4 weeks placebo)
- The mode of administration - oral tablet
Each subject will undergo treatment with Zibotentan and matched placebo for 4 weeks in a computer-generated random order (double-blind, crossover design) giving a total dosing period of 8 weeks. There will be a 2-week washout interval between the two treatment periods.
Participants will report the angina frequency through
Zinc Tablets - Nature's Own Australia - Dose - 30mg once daily - Duration - 8 weeks (4 weeks drug intervention and 4 weeks placebo) - The mode of administration - oral tablet Each subject will undergo treatment with Zibotentan and matched placebo for 4 weeks in a computer-generated random order (double-blind, crossover design) giving a total dosing period of 8 weeks. There will be a 2-week washout interval between the two treatment periods. Participants will report the angina frequency through an angina diary. The drug compliance will be assessed through drug tablet return.
Sponsors
The University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
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
For inclusion in the study subjects should fulfill the following criteria: a) Provision of informed consent prior to any study-specific procedures b) Female and/or male patients aged 18 years or older c) Documented angiographic features of the ANOCA as defined by TIMI-2 flow (i.e. requiring equal or more than 3 beats to opacify a major epicardial vessel) in the absence of obstructive CAD (i.e. no epicardial lesion equal or greater than 50%). d) Chest pain occurring more than or equal to 3 times/week in the preceding two weeks.
Exclusion criteria
a) Acute coronary syndrome admission within the preceding month, i.e. hospital admission for prolonged angina pain at rest associated with new ischaemic ECG changes and/or a rise in cardiac troponin level. b) Secondary causes of angina including: i. clinically significant anaemia (haemoglobin less than 100g/dL), ii. uncontrolled atrial fibrillation (i.e. ventricular response rate more than 108 bpm), iii. haemodynamically significant aortic stenosis (mean valve gradient more than or equal to 40mmHg). c) Patients with known concomitant disease with life expectance of less than 1 year. d) Abnormalities in liver function tests (ALT and/or AST more than equal to the upper limit of normal (ULN) or ALP more than or equal to ULN or Bilirubin more than or equal to 1.5 x ULN) e) Contraindication to any of the study treatments or known or suspected hypersensitivity to Zn. f) Patients with moderate to severe hepatic impairment g) Patients with moderate and severe renal failure (defined as a CLCR of less than 50 mL/minute determined using the Cockcroft-Gaul equation or by 24-hour CLCR), including patients undergoing renal dialysis h) Unwilling, or unable, to give informed consent. i) Concomitant participation in another clinical trial or research study (except where in the opinion of the Primary Investigator, the participant could benefit from enrolling in another trial)
Outcome results
None listed