Clinical trial NCT00948298: Effect of Vitamin D3 on Vascular Function
Official title: The Effect of Cholecalciferol (Vitamin D3) on Vascular Function and Cardiovascular Risk Factors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin D Deficiency
Keywords: cardiovascular disease
vitamin D
african american
low vitamin D levels
Lead sponsor: Charles Drew University of Medicine and Science
Sponsor class: OTHER
Collaborators: name: National Center for Research Resources (NCRR)
First posted: 2009-07-29
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Vitamin D is a natural nutrient. A little comes from our normal daily diet. Most of it comes from our skin after we have been in sunlight. If we have darker skin, we make less vitamin D. Vitamin D balances the calcium in our body. If our vitamin D levels get too low, it can cause health problems. It may increase our chance of getting high blood pressure or diabetes. Another problem we may have if our vitamin D levels are low is that our blood vessels may not work normally. These are important health problems for anyone. Because African Americans have darker skin, they are more likely than most other racial/ethnic groups to have low vitamin D levels. This study will look at treating African Americans with low vitamin D levels.

The goal of this study is to see how vitamin D helps blood vessels work. The investigators will do this study in African Americans who are overweight, have high blood pressure and have low vitamin D levels. The investigators will see if getting the vitamin D level to a normal value will improve how blood vessels work. The dose of vitamin D that will be given in this study is a high dose that is given to people with low vitamin D levels.

Detailed description: Cardiovascular Disease (CVD) and related disorders remain the leading cause of death in the nation. Hypovitaminosis D has been linked not only to several cardiovascular (CV) risk factors including hypertension, diabetes, obesity but also to increased rates of CVD. Thus,hypovitaminosis D presents a common pathway for a select subgroup with a clustering of CV risk factors in a profile that is predominant among ethnic minorities. Indeed, hypovitaminosis D is highly prevalent with an estimated 55% of the US adult population having levels at or below 30 ng/ml, and over 80% of African Americans having suboptimal values. Thus, we propose a twelve week randomized double-blind, placebo controlled pilot trial to assess the effect on vascular function and CV risk factors of 100,000 IU Vitamin D3 given every 4 weeks to overweight, hypertensive African-Americans with hypovitaminosis D. To our knowledge, the proposed project is the first to assess the effect of 'high-dose' Vitamin D3 administration on vascular function.We believe this study is also the first to examine the impact at a molecular level of Vitamin D3 repletion on the key mediators of cardio-metabolic pathways in humans. If our study results support our working hypothesis, we will be positioned to propose a larger scale study to detect a therapeutic effect on more definitive, clinical cardiovascular endpoints across a more diverse population.

Objectives:

1. Assess the role of Vitamin D3 treatment on vascular function in high risk subjects.

Primary Outcome: The primary outcome variable is pulse wave velocity (PWV, unit - m/s) for vascular stiffness assessed by radial artery tonometry (via SphygmoCor). The hypothesis for the primary analysis is that a greater increase in the PWV will occur in the Vitamin D3 treatment group than in the placebo group.

Secondary Outcome: Vascular/endothelial function as determined by measuring non-invasive vascular finger plethysmography (via EndoPat). Additional surrogates to be assessed as secondary markers of vascular/endothelial function include sitting and 24 hour ambulatory blood pressure measurements and spot urine protein/creatinine ratio.

Eligibility criteria: Inclusion Criteria:

* Males or females, 18-70 years of age and self-identified as African-American or Black
* Hypertension
* If a potential study patient is not on treatment, their systolic blood pressure (SBP) must be \> 130 mmHg, or diastolic blood pressure (DBP) \> 85 mmHg, and SBP must be \<160 mmHg and DBP must be \< 105 mmHg.
* If a potential study patient is on treatment then the SBP must be \<160 mmHg and DBP must be \< 105 mmHg
* Screening Vitamin D (D2 and D3 level) between 10 and 25 ng/ml (normal level \> 30 ng/ml)
* Body mass index (BMI) \> 25 kg/m2

Exclusion Criteria:

* Poorly controlled high blood pressure (SBP \>160 mmHg or DBP \> 105 mmHg)
* Diabetes (fasting blood sugar \> 125 mg/dl, or HbA1c \> 6.5%)
* Screening Vitamin D (D2 and D3 level) \< 10 ng/ml or \> 25 ng/ml
* Estimated glomerular filtration rate (eGFR) \< 45 ml/min
* Evidence of disease resulting in hypercalcemia
* History of kidney stones
* History of drug, alcohol, or illicit substance abuse within the past 6 months
* History of another chronic disease which the investigator feels should preclude the subject from entering the study
* Liver function tests (LFTs) greater than twice the upper limit of normal
* Subjects requiring chronic use of nonsteroidal anti-inflammatory drugs, aspirin, or other drugs that may affect the measurement of reactive oxidative species
* Subjects requiring treatment with other vitamin D preparations containing more than 400 IU of vitamin D
* Subjects requiring chronic use of immunosuppressive therapy or corticosteroids
* Recent (\< 6 months) myocardial infarction, stroke, or hospitalization for congestive heart failure
* Allergy/intolerance: known allergy to oral vitamin D or microcrystalline cellulose

Primary outcomes:
measure: Pulse Wave Velocity for Vascular Stiffness
timeFrame: 12 Weeks
Secondary outcomes:
measure: Changes in Sitting and 24 Ambulatory Blood Pressure
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Charles Drew University of Medicine and Science
name: David Martins, MD
role: PRINCIPAL_INVESTIGATOR
References: