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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypertension; Vitamin D Deficiency	Drug: calcitriol; Drug: Placebo	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Calcitriol (1α, 25-[OH]2 Vitamin D3) on Renin Expression in Hypertensive Patients Without Vitamin D Deficiency
• Study Start Date: May 2007
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Calcitriol	Drug: calcitriol; 1.0 mcg daily; Other Names: Rocaltrol; 1α, 25-[OH]2 Vitamin D3
Placebo Comparator: Placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. 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) ]

Secondary Outcome Measures :

1. Compare mononuclear leukocyte renin transcription (mRNA) between calcitriol and matched placebo. [ Time Frame: 13 MONTHS (MAY 2007-JUNE 2008) ]

Eligibility Criteria

• Ages Eligible for Study: 55 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

University of Utah

Investigators

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

More Information

• Responsible Party: mark munger, Professor, Pharmacotherapy, University of Utah
• ClinicalTrials.gov Identifier: NCT00585442
• Other Study ID Numbers: 22714; 10151812 ( Other Grant/Funding Number: American Foundation for Pharmaceutical Education )
• First Posted: January 3, 2008
• Last Update Posted: May 27, 2016
• Last Verified: March 2016

Additional relevant MeSH terms:

Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Vitamin D; Calcitriol; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents