Vitamin D Supplementation in Chronic Stable Heart Failure (VITD-HI)
|Heart Failure Vitamin D Deficiency||Drug: Cholecalciferol Drug: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Vitamin D Supplementation in Chronic Stable Heart Failure: a Randomized, Double-blind, Placebo-controlled Trial|
- NT-pro BNP [ Time Frame: month 0, 6 ]Change from Baseline in NT-pro BNP serum level at 6 months
- Percentage of patients with 25(OH)D ≥ 30 ng/ml at month 6 [ Time Frame: 6 months ]Percentage of patients with 25(OH)D ≥ 30 ng/ml at month 6
- Serum calcium [ Time Frame: month 0, 6 ]Serum calcium levels
- DXA [ Time Frame: month 0,12 ]Dual energy X-ray absorptiometry including body composition at month 0 and 12 (alternatively month 6)
- Urinary calcium [ Time Frame: month 0,6 ]Urinary calcium (spot urine)
|Study Start Date:||April 2011|
|Study Completion Date:||October 2013|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Placebo (herbal oil)
Placebo in matching volumes
Other Name: Herbal Oil
|Experimental: Vitamin D||
Cholecalciferol 90,000 IU followed by weekly 24,000 IU for 24 weeks of vitamin D3 (total dose: 666,000 IU)
Other Name: Vitamin D
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 . 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01292720
|Medical University of Graz|
|Graz, Austria, 8036|
|Principal Investigator:||Karin Amrein, MD||Medical University of Graz|