Effects of Vitamin D on Renin Expression in Hypertensive Patients

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00585442
• Other study ID #: 22714
• Secondary ID: 10151812
• Status: Terminated
• Phase: Phase 0
• First received: December 22, 2007
• Last updated: May 25, 2016
• Start date: May 2007
• Est. completion date: June 2008

Study information

• Verified date: March 2016
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years and older

Eligibility

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 1a, 25-(OH)2 vitamin D3 (calcitriol)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Vitamin D Deficiency

Intervention

Drug:
• calcitriol
1.0 mcg daily
• Placebo
Placebo

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare plasma renin activity (PRA) and plasma renin concentration (PRC) in hypertensive patients (JNC VII stage I) following 14 days treatment with calcitriol (1a, 25-[OH]2 vitamin D3) or matched placebo.		13 MONTHS (MAY 2007-JUNE 2008)	No
Secondary	Compare mononuclear leukocyte renin transcription (mRNA) between calcitriol and matched placebo.		13 MONTHS (MAY 2007-JUNE 2008)	No