Nesiritide in Hypertension

Summary

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, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) synthesis and secretion occur contributing to maintenance of optimal cardiorenal and blood pressure homeostasis. However, studies indicate that in subjects with cardiovascular diseases the biological structure of these hormones may be altered, thus reducing their favorable protective activities. New studies indicate that early and moderate hypertension is associated with a derangement of the natriuretic peptide system which is characterized by the lack of activation of biologically active ANP and BNP, while severe hypertension is characterized by cardiac release of altered molecular forms of ANP and BNP that have reduced biological properties and/or enhanced degradation.

The broad objective of this proposal is to advance the biology and therapeutics of the NPs with a special focus on the cardiac peptide BNP in human hypertension. Our proposal is based upon the biological properties of BNP (i.e. natriuretic, renin-angiotensin-aldosterone suppressing, vasodilating, anti-fibrotic, anti-hypertrophic and positive lusitropic), its mechanistic role in human hypertension, and thus its potential as an innovative chronic protein therapeutic to enhance the treatment of patients with hypertension. Importantly, BNP is an endocrine hormone normally produced by the human heart, and it has been approved for the treatment of acute heart failure in USA.

Conditions

• Hypertension

Interventions

DRUG

Nesiritide

This intervention is designed to determine the optimal dose range of BNP for treatment of patients with uncontrolled hypertension

DRUG

Placebo

For comparison to elucidate the true effect of nesiritide

Sponsors & Collaborators

• University of Oslo

  collaborator OTHER

• University Hospital, Akershus

  collaborator OTHER

• Oslo University Hospital

  lead OTHER

Principal Investigators

• Alessandro Cataliotti, MD, PhD · Oslo University Hospital and University of Oslo

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

79 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-12-31

Primary Completion

2018-12-31

Completion

2030-12-31

Countries

• Norway

Study Locations