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

Sponsored by:	University of Utah
Information provided by:	University of Utah
ClinicalTrials.gov Identifier:	NCT00585442

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
Hypertension Vitamin D Deficiency	Drug: calcitriol

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Vitamin D Ergocalciferol Cholecalciferol Calcitriol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Placebo Control, Parallel Assignment
Official Title:	Effects of Calcitriol (1α, 25-[OH]2 Vitamin D3) on Renin Expression in Hypertensive Patients Without Vitamin D Deficiency

Further study details as provided by 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Compare mononuclear leukocyte renin transcription (mRNA) between calcitriol and matched placebo. [ Time Frame: 13 MONTHS (MAY 2007-JUNE 2008) ] [ Designated as safety issue: No ]

Enrollment:	6
Study Start Date:	May 2007
Estimated Study Completion Date:	June 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental	Drug: calcitriol 1.0 mcg daily

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
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

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:	Univerisity of Utah ( University of Utah )
Study ID Numbers:	10151812, IRB# 00022714
Study First Received:	December 22, 2007
Last Updated:	January 2, 2008
ClinicalTrials.gov Identifier:	NCT00585442
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Vitamin D Deficiency
Calcium, Dietary
Cholecalciferol
Vitamin D
Malnutrition
Avitaminosis

Ergocalciferols
Vascular Diseases
Nutrition Disorders
Calcitriol
Deficiency Diseases
Hypertension

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Growth Substances
Physiological Effects of Drugs
Calcium Channel Agonists
Bone Density Conservation Agents
Cardiovascular Agents
Pharmacologic Actions

Membrane Transport Modulators
Vitamins
Therapeutic Uses
Vasoconstrictor Agents
Cardiovascular Diseases
Micronutrients

ClinicalTrials.gov processed this record on January 16, 2009