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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01292720
Recruitment Status : Completed
First Posted : February 9, 2011
Last Update Posted : May 28, 2014
Information provided by (Responsible Party):
Karin Amrein, MD, Medical University of Graz

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).

Condition or disease Intervention/treatment Phase
Heart Failure Vitamin D Deficiency Drug: Cholecalciferol Drug: Placebo Phase 3

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  (Clinical Trial)
Actual Enrollment : 29 participants
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
Study Start Date : April 2011
Actual Primary Completion Date : October 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo (herbal oil)
Drug: Placebo
Placebo in matching volumes
Other Name: Herbal Oil

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 Name: Vitamin D

Primary Outcome Measures :
  1. NT-pro BNP [ Time Frame: month 0, 6 ]
    Change from Baseline in NT-pro BNP serum level at 6 months

Secondary Outcome Measures :
  1. 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

  2. Serum calcium [ Time Frame: month 0, 6 ]
    Serum calcium levels

  3. DXA [ Time Frame: month 0,12 ]
    Dual energy X-ray absorptiometry including body composition at month 0 and 12 (alternatively month 6)

  4. Urinary calcium [ Time Frame: month 0,6 ]
    Urinary calcium (spot urine)

Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01292720

Medical University of Graz
Graz, Austria, 8036
Sponsors and Collaborators
Medical University of Graz
Principal Investigator: Karin Amrein, MD Medical University of Graz

Responsible Party: Karin Amrein, MD, Principal Investigator, Medical University of Graz Identifier: NCT01292720     History of Changes
Other Study ID Numbers: VITD-HI
First Posted: February 9, 2011    Key Record Dates
Last Update Posted: May 28, 2014
Last Verified: May 2014

Keywords provided by Karin Amrein, MD, Medical University of Graz:
vitamin D deficiency, vitamin D insufficiency, heart failure

Additional relevant MeSH terms:
Heart Failure
Vitamin D Deficiency
Heart Diseases
Cardiovascular Diseases
Deficiency Diseases
Nutrition Disorders
Vitamin D
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents