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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Vitamins
Vitamin D
Ergocalciferols
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on October 19, 2014