Effects of Vitamin D on Renin Expression in Hypertensive Patients

NCT ID: NCT00585442

Last Updated: 2016-05-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2008-06-30

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.

Conditions

Hypertension; Vitamin D Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Calcitriol

Group Type: EXPERIMENTAL

calcitriol

Intervention Type: DRUG

1.0 mcg daily

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

calcitriol

1.0 mcg daily

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Rocaltrol; 1α, 25-[OH]2 Vitamin D3

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)

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

mark munger

Professor, Pharmacotherapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Munger, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

10151812

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

22714

Identifier Type: -

Identifier Source: org_study_id