Vitamin D Supplementation in Chronic Stable Heart Failure

NCT ID: NCT01292720

Last Updated: 2014-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2013-10-31

Brief 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).

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.

Conditions

Heart Failure; Vitamin D Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo (herbal oil)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo in matching volumes

Vitamin D

Group Type: EXPERIMENTAL

Cholecalciferol

Intervention Type: DRUG

Cholecalciferol 90,000 IU followed by weekly 24,000 IU for 24 weeks of vitamin D3 (total dose: 666,000 IU)

Interventions

Cholecalciferol

Cholecalciferol 90,000 IU followed by weekly 24,000 IU for 24 weeks of vitamin D3 (total dose: 666,000 IU)

Intervention Type: DRUG

Placebo

Placebo in matching volumes

Intervention Type: DRUG

Other Intervention Names

Vitamin D; Herbal Oil

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Karin Amrein, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karin Amrein, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Graz

Locations

Medical University of Graz

Graz, , Austria

Countries

Austria

Other Identifiers

VITD-HI

Identifier Type: -

Identifier Source: org_study_id