Clinical trial NCT00585442: Effects of Vitamin D on Renin Expression in Hypertensive Patients
Official title: Effects of Calcitriol (1α, 25-[OH]2 Vitamin D3) on Renin Expression in Hypertensive Patients Without Vitamin D Deficiency
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Hypertension
Vitamin D Deficiency
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2008-01-03
Enrollment: 12
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: 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.
timeFrame: 13 MONTHS (MAY 2007-JUNE 2008)
Secondary outcomes:
measure: Compare mononuclear leukocyte renin transcription (mRNA) between calcitriol and matched placebo.
timeFrame: 13 MONTHS (MAY 2007-JUNE 2008)
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Mark Munger, PharmD
role: PRINCIPAL_INVESTIGATOR
References: