Vitamin D Supplementation in Chronic Stable Heart Failure

Heart Failure Clinical Trial

— VITD-HI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01292720
• Other study ID #: VITD-HI
• Status: Completed
• Phase: Phase 3
• First received: January 26, 2011
• Last updated: May 23, 2014
• Start date: April 2011
• Est. completion date: October 2013

Study information

• Verified date: May 2014
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 90 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Vitamin D Deficiency

Intervention

Drug:
• Cholecalciferol
Cholecalciferol 90,000 IU followed by weekly 24,000 IU for 24 weeks of vitamin D3 (total dose: 666,000 IU)
• Placebo
Placebo in matching volumes

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NT-pro BNP	Change from Baseline in NT-pro BNP serum level at 6 months	month 0, 6	No
Secondary	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	No
Secondary	Serum calcium	Serum calcium levels	month 0, 6	Yes
Secondary	DXA	Dual energy X-ray absorptiometry including body composition at month 0 and 12 (alternatively month 6)	month 0,12	No
Secondary	Urinary calcium	Urinary calcium (spot urine)	month 0,6	Yes