Vitamin D Supplementation in Chronic Stable Heart Failure (VITD-HI)

Vitamin D Supplementation in Chronic Stable Heart Failure: a Randomized, Double-blind, Placebo-controlled Trial

In cross-sectional and prospective cohort studies, vitamin D deficiency is associated with increased mortality, cardiovascular events including sudden cardiac death and stroke, diabetes, hypertension and impaired function of the immune and musculoskeletal system. The action of vitamin D on the cardiovascular system regulates cardiac function, endothelial and vascular smooth muscle, and, the renin-angiotensin system. Treatment with sufficiently high doses of vitamin D may represent a promising and inexpensive intervention option. To date, there are few data on the effect of cholecalciferol treatment in patients with chronic heart failure. The primary objective of this study is to investigate whether oral vitamin D supplementation improves chronic heart failure (measured with the surrogate parameter of NT-proBNP levels at month 0 and 6).

Study Overview

• Status: Completed
• Conditions: Heart Failure; Vitamin D Deficiency
• Intervention / Treatment: Drug: Placebo; Drug: Cholecalciferol

Detailed Description

A growing body of data suggests that low vitamin D levels may adversely affect cardiovascular health. For many cardiovascular events, seasonal variability with peak incidence in the winter months is proven. This may be attributable at least in part to declining body stores of vitamin D beginning with September. Recently, there have been several case reports about severe cardiomyopathy caused by vitamin D deficiency, especially in dark-skinned children who had low vitamin D levels. The heart is an important target organ for vitamin D, both on a genomic and nongenomic level. Myocytes express the vitamin D receptor and several models of hypertension in animal studies have shown that vitamin D treatment is able to prevent cardiac hypertrophy [9-10]. Vitamin D seems to inhibit activation of the cardiac renin-angiotensin system as well as the expression of genes involved in the development of myocardial hypertrophy. There is accumulating evidence that vitamin D deficiency may be an important factor in the development of congestive heart failure and sudden cardiac death.

In chronic hemodialysis patients, vitamin D supplementation has been associated with reduction of cardiac hypertrophy and a reduction of QT dispersion, the latter being considered a major risk factor for sudden cardiac death. A small study from 1984 showed an improvement in left ventricular function after treatment with cholecalciferol in hemodialysis patients. A recent study from our group has reported a negative correlation of 25(OH)D levels with NT-pro-BNP levels, New York Heart Association functional classes and impaired left ventricular function. Furthermore, hazard ratios for death attributable to heart failure and sudden cardiac death were 2.84 and 5.05, respectively, when patients with 25(OH)D <25ng/ml were compared with those having serum levels of 25(OH)D >75 ng/ml [11]. The anti-inflammatory properties of vitamin D also appear to play a role in congestive heart failure, as studied in a recent interventional trial. In animal models, vitamin D deficiency was proven to be associated with developing myocardial hypertrophy and fibrosis with aberrant cardiac contractility and relaxation. Moreover, vitamin D deficiency can raise parathyroid hormone secretion, which in turn may increase insulin resistance and be associated with the development of diabetes, hypertension and inflammation. In summary, vitamin D seems to exert a multitude of different effects all working in concert to protect the vascular and cardiac system by influencing various hierarchical levels of biologic response.

Recently, a randomized controlled trial in a subgroup of patients with heart failure(n=105, ≥ 70 years) was able to demonstrate a significant decrease in BNP levels at 10 and 20 weeks, while the primary endpoint "functional capacity" and quality of life did not differ between intervention and placebo group.

Because in this latter trial, even the intervention group did not reach normal vitamin D levels, we will use a higher dose of vitamin D given in shorter intervals.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic stable heart failure (NYHA II-IV, ejection fraction ≤ 40%)
• ≥ 45 years
• 25 (OH) Vitamin D ≤ 30ng/ml

Exclusion Criteria:

• hypercalcemia (total serum calcium > 2.65 mmol/l OR ionized calcium > 1.35 mmol/l)
• nephro-/urolithiasis (≤1 year)
• known granulomatous diseases (active tuberculosis, sarcoidosis)
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D	Drug: Cholecalciferol; Cholecalciferol 90,000 IU followed by weekly 24,000 IU for 24 weeks of vitamin D3 (total dose: 666,000 IU); Other Names: Vitamin D
Placebo Comparator: Placebo; Placebo (herbal oil)	Drug: Placebo; Placebo in matching volumes; Other Names: Herbal Oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NT-pro BNP	Change from Baseline in NT-pro BNP serum level at 6 months	month 0, 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with 25(OH)D ≥ 30 ng/ml at month 6	Percentage of patients with 25(OH)D ≥ 30 ng/ml at month 6	6 months
Serum calcium	Serum calcium levels	month 0, 6
DXA	Dual energy X-ray absorptiometry including body composition at month 0 and 12 (alternatively month 6)	month 0,12
Urinary calcium	Urinary calcium (spot urine)	month 0,6

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Karin Amrein, MD, Medical University of Graz

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: January 26, 2011
• First Submitted That Met QC Criteria: February 8, 2011
• First Posted (Estimate): February 9, 2011

Study Record Updates

• Last Update Posted (Estimate): May 28, 2014
• Last Update Submitted That Met QC Criteria: May 23, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: vitamin D deficiency, vitamin D insufficiency, heart failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Heart Failure; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: VITD-HI