Effects of Vitamin D on Renin Expression in Hypertensive Patients

Utah System of Higher Education (USHE)

Status and phase: Terminated; Early Phase 1

Conditions: Hypertension; Vitamin D Deficiency

Treatments: Drug: Placebo; Drug: calcitriol

Study type: Interventional

Funder types: Other

Identifiers

NCT00585442

22714

10151812 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 2 patient groups, including a placebo group

Calcitriol

Experimental group

Treatment:

Drug: calcitriol

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo