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

This study has been completed.
Sponsor:
Collaborator:
Netherlands Foundation for Cardiovascular Excellence
Information provided by (Responsible Party):
Willem-Peter Theodoor Ruifrok, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01092130
First received: March 12, 2010
Last updated: February 13, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Chronic Heart Failure
Drug: Vitamin D
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Blinded-endpoint, Randomized, Prospective Trial Investigating the Effects of Vitamin D Administration on Plasma Renin Activity in Patients With Stable Chronic Heart Failure

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Plasma Renin Activity [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The primary endpoint of this study is the PRA after 6 weeks of treatment with vitamin D compared to the PRA after 6 weeks without treatment.


Secondary Outcome Measures:
  • Safety endpoints are biochemical indices of kidney function and bone homeostasis [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • To evaluate the effect of vitamin D administration on plasma values of additional markers of renin-angiotensin system activity, including angiotensin II, angiotensin converting enzyme activity and chymase activity [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • To evaluate the effect of vitamin D administration on different markers of the vitamin D cascade, such as vitamin D, calcium, phosphate and PTH (parathyroid hormone) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • To evaluate the effect of vitamin D administration on plasma levels of NT-proBNP [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • To evaluate the effect of vitamin D administration on urinary levels of markers of glomerular and tubular damage [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • To evaluate the effect of vitamin D administration on extracellular matrix markers (PIIINP, PICP, PINP) and degradation markers (MMP1, MMP9, TIMP1, MMP1/TIMP1-complex) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • To evaluate the effect of vitamin D administration on NYHA-class [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 101
Study Start Date: March 2010
Study Completion Date: September 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Vitamin D
2000 IU vitamin D daily, for 6 weeks
Other Name: Colecalciferol

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01092130

Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700 RB
Sponsors and Collaborators
University Medical Centre Groningen
Netherlands Foundation for Cardiovascular Excellence
Investigators
Principal Investigator: W. T. Ruifrok, MD University Medical Centre Groningen
Study Director: R. A. de Boer, MD, PhD University Medical Centre Groningen
Study Chair: W. H. van Gilst, PhD University Medical Centre Groningen
  More Information

Additional Information:
No publications provided by University Medical Centre Groningen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Willem-Peter Theodoor Ruifrok, MD, PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01092130     History of Changes
Other Study ID Numbers: WTR-ECG-4
Study First Received: March 12, 2010
Last Updated: February 13, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
Heart failure
Vitamin D
Plasma renin activity
Renin angiotensin system

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Vitamin D
Ergocalciferols
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 14, 2014