Human Brain Natriuretic Peptide (BNP) (or Nesiritide) to Help Heart, Kidney and Humoral Function.

Phase 1

Completed

Brief Summary: The purpose of this research study is to evaluate the effects of cardiac hormone replacement with SQ (subcutaneous or under the skin) injection of BNP (brain natriuretic peptide, a hormone produced by the heart) on the pumping ability of the heart, kidney function and levels of different hormones in the blood in response to an intravenous salt solution.

Detailed Description: Prior to initiation of the study, subjects will be stabilized for at least one week on a no added salt diet (120 milliequivalent (mEq) Na/Day) which will be maintained during the study. Participants in this study will be randomized to receive BNP or placebo (an inactive, saline shot). The participant will need to give themselves a shot in their stomach (similar to diabetics giving themselves insulin) twice a day for twelve weeks. The study requires a screening visit to determine eligibility and discuss the study. At this visit a blood draw for heart and liver function and a six minute walk will be done. There will also be two other outpatient visits and two inpatient stays, for 48 hours, in the Clinical Research Unit at St. Marys Hospital. During the two overnight stays, blood and urine samples will be done to get heart and kidney function as well as a research echocardiogram. An acute saline load (0.9% normal saline 1.25 ml/kg/min for 1 hour) will be given and blood and urine samples collected After enrollment, the study lasts for twelve weeks. It is planned to treat 2 subjects with active drug per each placebo subject to improved the precision of between group comparison.

Recruitment & Eligibility

Inclusion Criteria

Subjects with ejection fraction of greater than 50% with moderate or severe diastolic dysfunction as assessed by Doppler echocardiography
No signs or symptoms of congestive heart failure and who have not been hospitalized for heart failure

Exclusion criteria:

Myocardial Infarction (MI) within 3 months of screening
Unstable angina within 14 days of screening, or any evidence of myocardial ischemia
Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
Severe congenital heart diseases
Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
Second or third degree heart block without a permanent cardiac pacemaker
Stroke within 3 months of screening, or other evidence of significantly compromised central nervous system (CNS) perfusion
Total bilirubin of > 1.5 mg/dL or other liver enzymes > 1.5 times the upper limit of normal (mg/dL = milligrams per deciliter)
Serum creatinine of > 3.0 mg/dL
Serum sodium of < 125 mEq/dL or > 160 mEq/dL (milliequivalents per deciliter)
Serum potassium of < 3.5 mEq/dL or > 5.0/dL
Serum digoxin level of > 2.0 ng/ml (nanograms per milliliter)
Systolic pressure of < 85 mm Hg (millimeters of mercury)
Hemoglobin < 10 gm/dl (grams per deciliter)

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
BNP (nesiritide)	BNP (nesiritide)	BNP 10 micrograms/Kg twice per day given subcutaneously for 12 weeks
Placebo	Placebo	Saline solution given subcutaneously twice per day for 12 weeks (packaged to match active comparator)

Primary Outcome Measures

Name	Time	Method
Change in Urinary Sodium Excretion in Response to Saline Load	Baseline, 12 weeks	Renal (or kidney) function was measured by the sodium or salt in the urine, following administration of a pre-specified amount of saline (salt).

Secondary Outcome Measures

Name	Time	Method
Change in Urinary Flow in Response to Saline Load	Baseline, 12 weeks	Urinary flow is a measure of renal (or kidney) function and was measured in milliliters per minute.
Change in Glomerular Filtration Rate (GFR) in Response to Saline Load	Baseline, 12 weeks	Renal or kidney function was measured by GFR determined by iothalamate clearance. GFR describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m\^2 of body surface area. A lower GFR means the kidney is not filtering normally. An estimated GFR of less than 60 mg/ml/1.73 m\^2 of body surface area is considered to be impaired kidney function.
Left Ventricular (LV) Filling Pressure	Baseline, 12 weeks	LV diastolic function as measured by Doppler echocardiography. E/e' is the ratio of the mitral inflow velocity (E) to the mitral annulus tissue Doppler velocity (e'). A decrease in the ratio indicates a lower filling pressure and improved LV diastolic function.