study to investigate the effects of vitamin d administration on plasma renin activity in patients with stable chronic heart failure

Conditions: Chronic Heart Failure

Summary: the renin-angiotensin system (ras) is a regulatory system that plays an essential role in patients with chronic heart failure (chf). plasma renin activity (pra) is a strong and independent predictor of outcome, also in the presence of ace inhibitors (ace-i) and/or angiotensin receptor blockers (arbs). recently, it has been shown that vitamin d regulates renin transcription by activating the vitamin d receptor (vdr). thus, specific activation of the vdr represents a novel target for therapeutic intervention in chf. currently, clinical data are lacking. the investigators aim to investigate the effect of the administration of vitamin d in patients with chf.


Eligibility criteria:
inclusion criteria: * out clinical patients ≥ 18 years of age, male or female. * patients with a diagnosis of chronic heart failure (nyha class ii, iii or iv). * patients must at least be treated with an ace-i at a stable dose (at least enalapril 10 mg daily or any other ace-i, e.g. ramipril, quinapril, lisinopril, fosinopril, perindopril, trandolapril; on equivalent doses, or maximum tolerated dose) or if intolerant to ace-i with arb therapy (candesartan 8 mg daily or any other arb in equivalent dose, or maximum tolerated dose) for at least 4 weeks prior to visit 1. * patients must be treated with a beta blocker unless contraindicated or not tolerated at a stable dose for at least 4 weeks prior to visit 1 (for patients not on target dose or in absence of that medication, the reason should be documented). * concomitant use of ace-i and/or arb and/or aldosterone antagonist is permitted. exclusion criteria: * lvef \>45% at visit 1 (local measurement, measured within the past 12 months assessed by echocardiogram, muga or ventricular angiography). * history of hypersensitivity to the study drugs. * patients with phenylketonuria. * patients with fructose intolerance. * current acute decompensated heart failure. * hypercalcemia (\>2.65 mmol/l, corrected for albumin). * hypercalciuria. * estimated glomerular filtration fraction (egfr) between 30 and 60 ml/min/1.73m2 as measured by the modified of diet in renal disease (mdrd) formula. * nephrolithiasis. * sarcoidosis. * use of the following medication: corticosteroids, thyroxin, anti epileptic drugs, tetracyclines, quinolones * intake of supplements containing vitamin d and/or calcium. * acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major vascular surgery, percutaneous coronary intervention (pci) or carotid angioplasty, within the past 3 months. * coronary or carotid artery disease likely to require surgical or pci. * right heart failure due to severe pulmonary disease. * diagnosis of peripartum or chemotherapy induced cardiomyopathy within the last year. * patients with a history of heart transplant or who are on a transplant list or with lvad device (left ventricular assistance device). * documented ventricular arrhythmia with syncopal episodes within past 3 months that is untreated. * documented history of ventricular tachycardia or ventricular fibrillation without icd (internal cardiac defibrillator). * symptomatic bradycardia, or second or third degree heart block without a pacemaker. * implantation of a crt (cardiac resynchronization therapy) device within prior 3 months. * presence of hemodynamically significant mitral and /or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation. * presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis. * any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs. * any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase. * primary liver disease considered to be life threatening. * currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to visit 1. * history or presence of any other diseases (i.e. including malignancies) with a life expectancy of \< 5 years. * current double-blind treatment in heart failure (hf) trials. * participation in an investigational drug study at the time of enrollment or within the past 30 days or 5 half lives of enrollment whichever is longer. * any surgical or medical condition that in the opinion of the investigator or medical monitor would jeopardize the evaluation of efficacy or safety. * history of noncompliance to medical regimens and patients who are considered potentially unreliable. * pregnant or lactating women. * treatment with any of the following drugs within the past 4 weeks prior to visit 1 (t0): * direct renin inhibition including aliskiren * intravenous vasodilator and/or inotropic drugs

Keywords: heart failure vitamin d plasma renin activity renin angiotensin system