Study to Investigate the Effects of Vitamin D Administration on Plasma Renin Activity in Patients With Stable Chronic Heart Failure

NCT ID: NCT01092130

Last Updated: 2013-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2012-09-30

Brief 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.

Conditions

Chronic Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vitamin D

Patients were randomized by an automated computer system to 2000 IU oral cholecalciferol once daily or control (i.e. no extra medication), in a 1:1 ratio for a period of six weeks. Blood was collected in a sitting position on visits 2-4 and patients were asked to collect 24h urine samples prior to visits 2 and 4. Heart failure medication was maintained unchanged throughout the trial. Changes in diuretic dose were permitted if necessary to treat decompensation or renal dysfunction.

Group Type: EXPERIMENTAL

Vitamin D

Intervention Type: DRUG

2000 IU vitamin D daily, for 6 weeks

Interventions

Vitamin D

2000 IU vitamin D daily, for 6 weeks

Intervention Type: DRUG

Other Intervention Names

Colecalciferol

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Netherlands Foundation for Cardiovascular Excellence

UNKNOWN

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Willem-Peter Theodoor Ruifrok

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

W. T. Ruifrok, MD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

R. A. de Boer, MD, PhD

Role: STUDY_DIRECTOR

University Medical Center Groningen

W. H. van Gilst, PhD

Role: STUDY_CHAIR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, Provincie Groningen, Netherlands

Countries

Netherlands

References

Schroten NF, Ruifrok WP, Kleijn L, Dokter MM, Sillje HH, Lambers Heerspink HJ, Bakker SJ, Kema IP, van Gilst WH, van Veldhuisen DJ, Hillege HL, de Boer RA. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: an open-label, blinded end point, randomized prospective trial (VitD-CHF trial). Am Heart J. 2013 Aug;166(2):357-364.e2. doi: 10.1016/j.ahj.2013.05.009. Epub 2013 Jun 24.

Reference Type: DERIVED

PMID: 23895820 (View on PubMed)

Other Identifiers

WTR-ECG-4

Identifier Type: -

Identifier Source: org_study_id