Hypertension, Vitamin D Deficiency
Conditions
Brief summary
The cardiovascular effects of vitamin D therapy (in humans) have been documented only in patients with known vitamin D deficiency or hyperparathyroidism (a surrogate marker of inadequate vitamin D activity). It is unknown whether the cardiovascular benefits of vitamin D therapy extend beyond these patients to the general hypertensive population. We propose to directly measure the effect of vitamin D therapy on plasma renin activity (PRA), plasma renin concentration (PRC), renin transcription (in mononuclear leukocytes), and blood pressure in hypertensive (but otherwise healthy) patients in a randomized, controlled, experimental trial. This will be the first study to assess vitamin D receptor (VDR) biological (PRA, PRC, renin mRNA, and polymorphisms) and hypertensive activity in patients without vitamin D deficiency. We hypothesize that vitamin D inhibition of renin transcription will produce significant reductions in PRA, PRC, renin transcription, inflammatory cytokines, SBP, and DBP, with potential variation by VDR genotype. Such a result may prove to be significant in the treatment of hypertension, as even modest blood pressure reductions (5 mmHg) are associated with a 14% reduction in mortality due to stroke, a 9% reduction in mortality due to CHD, and a 7% overall reduction in all-cause mortality.
Interventions
DRUGcalcitriol
1.0 mcg daily
DRUGPlacebo
Placebo
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients age \> 55 years. 2. Female patients must be postmenopausal, as determined by surgical hysterectomy or 12 month history since last active menstruation 3. Stage I hypertension (JNC VII Criteria): mean systolic blood pressure (mSBP) 140-159 mmHg and mean diastolic blood pressure 90 - 99 mmHg (mDBP)2 4. Provide informed consent
Exclusion criteria
1. Serum vitamin D \<55 pmol/L 2. Serum calcium \>10.5 mg/dL 3. Serum phosphate (inorganic) \>5.5 mg/dL 4. Serum parathyroid hormone (PTH) \>1.3 pmol/L 5. Vitamin D supplements, calcium supplements, estrogen replacement therapy, corticosteroids (inhaled/oral), or hydroxymethyl glutarate CoA reductase inhibitors (statins) within 30 days prior to randomization 6. Stage II hypertension (JNC VII criteria): mSSBP \>160 mmHg or mSDBP \>100 mmHg 7. Use of alpha2-agonists, beta-blockers, or more than 2 anti-hypertensive medications at screening 8. Estimated creatinine clearance \<30 mL/min by Crockroft-Gault Formula 9. History of heart failure (HF), acute myocardial infarction (AMI), acute coronary syndrome (ACS), transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral vascular disease (PVD), or known clotting disorder 10. Insulin dependent diabetes mellitus (patients stabilized on oral regimens may be enrolled) 11. History of hypersensitivity reaction to 1α, 25-(OH)2 vitamin D3 (calcitriol)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare plasma renin activity (PRA) and plasma renin concentration (PRC) in hypertensive patients (JNC VII stage I) following 14 days treatment with calcitriol (1α, 25-[OH]2 vitamin D3) or matched placebo. | 13 MONTHS (MAY 2007-JUNE 2008) |
Secondary
| Measure | Time frame |
|---|---|
| Compare mononuclear leukocyte renin transcription (mRNA) between calcitriol and matched placebo. | 13 MONTHS (MAY 2007-JUNE 2008) |
Countries
United States
Outcome results
None listed