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

To Define in Human Preclinical Diastolic Dysfunction (PDD) the Actions of Chronic Administration of Subcutaneous (SQ) BNP on the Left Ventricular, Renal and Humoral Function and on the Integrated Response to Acute Sodium Loading

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.

Study Overview

• Status: Completed
• Conditions: Left Ventricular Diastolic Dysfunction
• Intervention / Treatment: Drug: Placebo; Drug: BNP (nesiritide)

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2; 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 and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: BNP (nesiritide); BNP 10 micrograms/Kg twice per day given subcutaneously for 12 weeks	Drug: BNP (nesiritide); Other Names: nesiritide; natrecor
PLACEBO_COMPARATOR: Placebo; Saline solution given subcutaneously twice per day for 12 weeks (packaged to match active comparator)	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Urinary Flow in Response to Saline Load	Urinary flow is a measure of renal (or kidney) function and was measured in milliliters per minute.	Baseline, 12 weeks
Change in Glomerular Filtration Rate (GFR) in Response to Saline Load	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.	Baseline, 12 weeks
Left Ventricular (LV) Filling Pressure	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.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); National Center for Research Resources (NCRR); Scios, Inc.

Publications and helpful links

General Publications

• Wan SH, McKie PM, Schirger JA, Slusser JP, Hodge DO, Redfield MM, Burnett JC Jr, Chen HH. Chronic Peptide Therapy With B-Type Natriuretic Peptide in Patients With Pre-Clinical Diastolic Dysfunction (Stage B Heart Failure). JACC Heart Fail. 2016 Jul;4(7):539-547. doi: 10.1016/j.jchf.2015.12.014. Epub 2016 Feb 10.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: November 29, 2006
• First Submitted That Met QC Criteria: November 29, 2006
• First Posted (ESTIMATE): November 30, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): July 1, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Ventricular Dysfunction, Left; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, Brain
• Other Study ID Numbers: 05-004190; P01HL076611 (U.S. NIH Grant/Contract); UL1RR024150 (U.S. NIH Grant/Contract)