Effects of Vitamin D on Renin Expression in Hypertensive Patients

Study Overview
=================
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.

Official Title
-----------------
Effects of Calcitriol (1α, 25-[OH]2 Vitamin D3) on Renin Expression in Hypertensive Patients Without Vitamin D Deficiency

Conditions
-----------------
Hypertension, Vitamin D Deficiency

Intervention / Treatment
-----------------
* Drug: calcitriol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients age > 55 years. Female patients must be postmenopausal, as determined by surgical hysterectomy or 12 month history since last active menstruation Stage I hypertension (JNC VII Criteria): mean systolic blood pressure (mSBP) 140-159 mmHg and mean diastolic blood pressure 90 - 99 mmHg (mDBP)2 Provide informed consent Exclusion Criteria: Serum vitamin D <55 pmol/L Serum calcium >10.5 mg/dL Serum phosphate (inorganic) >5.5 mg/dL Serum parathyroid hormone (PTH) >1.3 pmol/L Vitamin D supplements, calcium supplements, estrogen replacement therapy, corticosteroids (inhaled/oral), or hydroxymethyl glutarate CoA reductase inhibitors (statins) within 30 days prior to randomization Stage II hypertension (JNC VII criteria): mSSBP >160 mmHg or mSDBP >100 mmHg Use of alpha2-agonists, beta-blockers, or more than 2 anti-hypertensive medications at screening Estimated creatinine clearance <30 mL/min by Crockroft-Gault Formula 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 Insulin dependent diabetes mellitus (patients stabilized on oral regimens may be enrolled) History of hypersensitivity reaction to 1α, 25-(OH)2 vitamin D3 (calcitriol)

Ages Eligible for Study
-----------------
Minimum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcitriol<br> | Drug: calcitriol<br>* 1.0 mcg daily<br>* Other names: 1α, 25-[OH]2 Vitamin D3;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare mononuclear leukocyte renin transcription (mRNA) between calcitriol and matched placebo. |  | 13 MONTHS (MAY 2007-JUNE 2008) |