Effects of Vitamin D on Renin Expression in Hypertensive Patients

• ClinicalTrials.gov Identifier: NCT00585442
• Recruitment Status: Terminated
• First Posted: January 3, 2008
• Last Update Posted: May 27, 2016
• Sponsor: University of Utah
• Information provided by (Responsible Party): mark munger, University of Utah

Tracking Information

• First Submitted Date: December 22, 2007
• First Posted Date: January 3, 2008
• Last Update Posted Date: May 27, 2016
• Study Start Date: May 2007
• Actual Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 2, 2008): 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. [ Time Frame: 13 MONTHS (MAY 2007-JUNE 2008) ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: January 2, 2008): Compare mononuclear leukocyte renin transcription (mRNA) between calcitriol and matched placebo. [ Time Frame: 13 MONTHS (MAY 2007-JUNE 2008) ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hypertension
• Vitamin D Deficiency

Intervention

• Drug: calcitriol
  1.0 mcg daily
  Other Names:

  • Rocaltrol
  • 1α, 25-[OH]2 Vitamin D3
• Drug: Placebo
  Placebo

Study Arms

• Experimental: Calcitriol
  Intervention: Drug: calcitriol
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 25, 2016): 12
• Original Actual Enrollment (submitted: January 2, 2008): 6
• Actual Study Completion Date: June 2008
• Actual Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00585442
• Other Study ID Numbers: 22714; 10151812 ( Other Grant/Funding Number: American Foundation for Pharmaceutical Education )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: mark munger, University of Utah
• Study Sponsor: University of Utah
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mark Munger, PharmD; University of Utah

• PRS Account: University of Utah
• Verification Date: March 2016