B-type Natriuretic Peptide (BNP) in Human Hypertension

Clinical Proteomics and Protein Therapeutics in Human Hypertension (BNP in Human Hypertension - Phase 1)

The investigators working hypothesis is that human hypertension is in part due to a derangement in the endocrine function of the heart - a primary or secondary mechanism - resulting in a relative deficiency of the natriuretic peptides (NP). The remodeled hypertensive heart could result in altered processing and degradation of B-type NP resulting in altered molecular forms with decreased biological activity. The investigators further hypothesized the chronic administration of BNP in subjects with hypertension, is feasible, safe and will induce a sustained reduction in blood pressure.

Study Overview

• Status: Terminated
• Conditions: Hypertension Stage 1
• Intervention / Treatment: Drug: brain natriuretic peptide; Other: no-added salt diet

Detailed Description

Ongoing investigations by our laboratory group and others have established that the heart is an endocrine organ as well as a pump. The heart synthesizes and secretes two peptide hormones - atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) - that are endogenous ligands for a particulate guanylyl cyclase receptor (NPR-A). Following receptor binding and generation of its second messenger cGMP, the natriuretic peptides (NPs) mediate biological actions which include natriuresis, inhibition of the renin-angiotensin system and vasodilatation with local autocrine and paracrine actions in the heart to include inhibition of fibrosis and enhancement of diastolic function.

Hypertension remains a global burden in cardiovascular disease leading to stroke, myocardial infarction and heart failure. Its myocardial complications result from increased mechanical load on the heart. Under physiological conditions of increased myocardial load and resulting myocardial stretch, ANP and BNP synthesis and secretion occur contributing to maintenance of optimal cardiorenal and blood pressure homeostasis.

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years.
• Subjects with stage 1 hypertension (SBP: 140-159 mm Hg or DBP 90-99 mm Hg) If on therapy, it must be stable for at least 1 month.

Exclusion Criteria:

• Congestive Heart Failure (any NYHA class).
• EF < 50%.
• Myocardial infarction within 3 months of screening.
• Unstable angina within 14 days of screening, or any evidence of myocardial ischemia.
• Moderate to severe pulmonary hypertension.
• Valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis.
• Sustained VT or V-fib within 14 days of screening.
• Sustained Atrial Fibrillation.
• Second or third degree AV block without a permanent cardiac pacemaker.
• CVA within 3 months of screening, or other evidence of significantly compromised CNS perfusion.
• Total bilirubin of >1.5 mg/dL or AST and ALT 1.5 times the upper limit of normal range.
• Renal insufficiency assessed by calculated GFR < 60 ml/min (Cockroft-Gault equation).
• Serum sodium of < 125 mEq/dL or > 160 mEq/dL.
• Serum potassium of < 3.5 mEq/dL or > 5.0 mEq/dL.
• Women taking hormonal contraceptives.
• Body Mass Index (BMI) > 35.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The blood pressure will decrease with BNP injections	during study intervention

Collaborators and Investigators

• Sponsor: Mayo Clinic

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: April 2, 2009
• First Submitted That Met QC Criteria: August 5, 2009
• First Posted (Estimate): August 6, 2009

Study Record Updates

• Last Update Posted (Estimate): October 12, 2011
• Last Update Submitted That Met QC Criteria: October 10, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: hypertension treatment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, Brain
• Other Study ID Numbers: 06-003032; MC cardiorenal lab funds