Natriuretic Peptide System as Therapy in Human Preclinical Left Ventricle Dysfunction

What Was Tested

This registered phase 1, phase 2 trial tested BNP (Nesiritide).

The action of this hormone is called the natriuretic response.

It had two arms (groups): Placebo First, then Nesiritide (Arm A) (experimental) and Nesiritide First, then Placebo (Arm B) (experimental).

In the first intervention period the subjects received subcutaneous placebo given in the abdomen. After a lead in period of 15 minutes, the acute saline load was administered. There was a 2 week washout period. In the second intervention period, the subjects received subcutaneous nesiritide given in the abdomen. After a lead in period of 15 minutes, the acute saline load was administered.

In the first intervention period the subjects received subcutaneous nesiritide given in the abdomen. After a lead in period of 15 minutes, the acute saline load was administered. There was a 2 week washout period. In the second intervention period, the subjects received subcutaneous placebo given in the abdomen. After a lead in period of 15 minutes, the acute saline load was administered.

The registry classes the interventions as drug.

More on the Plan

The broad objective of this study is to define the integrated cardiorenal response to acute volume expansion (VE) in humans with presystolic dysfunction (PSD), prediastolic dysfunction (PDD), and normal cardiac function.

The researchers hypothesized that there is an impaired cardiorenal endocrine response to acute VE in PSD and PDD which is characterized by the lack of appropriate activation of urinary cGMP and urinary sodium excretion.

Further, the researchers hypothesized that PSD, PDD, and normal control subjects would respond similarly to exogenous administration B-type natriuretic peptide (BNP).

The natriuretic peptides (NPs) are a family of structurally similar but genetically distinct peptides with vasodilating, natriuretic, renin inhibiting, and lusitropic properties.

Who Took Part

The registry lists 58 actual participants took part.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Normal Doppler diastolic function with no clinical signs or symptoms. History of cardiovascular and renal disease. No prior use of any cardiovascular medications. Ability to perform a 6-minute walk of \> 450 meters. Ability to perform a 6-minute walk of \> 450 meters.

The full record lists 14 inclusion and 18 exclusion criteria; among the exclusions: myocardial infarction within 3 months of screening; unstable angina within 14 days of screening, or any evidence of myocardial ischemia; sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening.

How the Study Was Run

Design: randomized, crossover and triple-blind.

Because people in this BNP (Nesiritide) study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

In the crossover set-up each of the participants took both BNP (Nesiritide) and the comparison in turn, acting as their own control.

Neither the participants nor the staff measuring them knew who was on BNP (Nesiritide), so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider and investigator.

It started in 2006-02 with completion listed for 2008-08.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

Researchers chose this as the main measure: Change in Natriuresis (Urinary Sodium Excretion) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment (time frame: baseline and 60 minutes). Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) (time frame: Baseline, 30 min, 60 min). Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) (time frame: Baseline, 30 min, 60 min).

What This Means in Plain Language

Put simply, this is a phase 1, phase 2, randomized trial of BNP (Nesiritide) in 58 people.

The trial is marked completed; results are posted on the registry, and this page does not restate them.

More context: the BNP (Nesiritide) compound page, all human trials.