B-type Natriuretic Peptide (BNP) in Human Hypertension

NCT ID: NCT00953472

Last Updated: 2011-10-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2011-04-30

Brief Summary

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.

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.

Conditions

Hypertension Stage 1

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

brain natriuretic peptide

start 10 mcg/kg (2 participants), 7 mcg/kg (2 participants), 5 mcg/kg (2 participants) and 2 mcg/kg (2 participants)

Intervention Type: DRUG

no-added salt diet

instruction to reduce salt for one week prior to study

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

MC cardiorenal lab funds

Identifier Type: -

Identifier Source: secondary_id

06-003032

Identifier Type: -

Identifier Source: org_study_id