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

NCT01092130 | Completed Phase 2 DMC

• 1 other identifier: WTR-ECG-4
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

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

Keywords

Heart failure; Vitamin D; Plasma renin activity; Renin angiotensin system

Outcome Measures

Primary Outcomes (1)

• Plasma Renin Activity

  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.

  6 weeks

Secondary Outcomes (7)

• Safety endpoints are biochemical indices of kidney function and bone homeostasis

  6 weeks

• 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

  6 weeks

• 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)

  6 weeks

• To evaluate the effect of vitamin D administration on plasma levels of NT-proBNP

  6 weeks

• To evaluate the effect of vitamin D administration on urinary levels of markers of glomerular and tubular damage

  6 weeks

Study Arms (1)

Vitamin D

EXPERIMENTAL

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

Interventions

Vitamin D DRUG

2000 IU vitamin D daily, for 6 weeks

Also known as: Colecalciferol

Vitamin D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Netherlands Foundation for Cardiovascular Excellence: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, Provincie Groningen, 9700 RB, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 23895820 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Vitamin D; Cholecalciferol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids

Study Officials

• W. T. Ruifrok, MD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• R. A. de Boer, MD, PhD

  University Medical Center Groningen

  STUDY DIRECTOR

• W. H. van Gilst, PhD

  University Medical Center Groningen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: March 12, 2010
• First Posted: March 24, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: September 1, 2012
• Last Updated: February 15, 2013

Record last verified: 2013-02

Locations

NL (1)