Effects of Vitamin D on Renin Expression in Hypertensive Patients - Full Text View

Purpose

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	Intervention	Phase
Hypertension Vitamin D Deficiency	Drug: calcitriol Drug: Placebo	Early Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Vitamin D Vitamin D Deficiency

Drug Information available for: Vitamin D Calcitriol

U.S. FDA Resources

Further study details as provided by mark munger, University of Utah:

Primary Outcome Measures:

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:

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


Enrollment:	12
Study Start Date:	May 2007
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Calcitriol	Drug: calcitriol 1.0 mcg daily Other Names: Rocaltrol 1α, 25-[OH]2 Vitamin D3
Placebo Comparator: Placebo	Drug: Placebo Placebo

Eligibility


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

Criteria

Inclusion Criteria:

Male or female patients age > 55 years.
Female patients must be postmenopausal, as determined by surgical hysterectomy or 12 month history since last active menstruation
Stage I hypertension (JNC VII Criteria): mean systolic blood pressure (mSBP) 140-159 mmHg and mean diastolic blood pressure 90 - 99 mmHg (mDBP)2
Provide informed consent

Exclusion Criteria:

Serum vitamin D <55 pmol/L
Serum calcium >10.5 mg/dL
Serum phosphate (inorganic) >5.5 mg/dL
Serum parathyroid hormone (PTH) >1.3 pmol/L
Vitamin D supplements, calcium supplements, estrogen replacement therapy, corticosteroids (inhaled/oral), or hydroxymethyl glutarate CoA reductase inhibitors (statins) within 30 days prior to randomization
Stage II hypertension (JNC VII criteria): mSSBP >160 mmHg or mSDBP >100 mmHg
Use of alpha2-agonists, beta-blockers, or more than 2 anti-hypertensive medications at screening
Estimated creatinine clearance <30 mL/min by Crockroft-Gault Formula
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
Insulin dependent diabetes mellitus (patients stabilized on oral regimens may be enrolled)
History of hypersensitivity reaction to 1α, 25-(OH)2 vitamin D3 (calcitriol)

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00585442

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 History of Changes
Other Study ID Numbers:	22714 10151812 ( Other Grant/Funding Number: American Foundation for Pharmaceutical Education )
Study First Received:	December 22, 2007
Last Updated:	May 25, 2016

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on June 21, 2017