Clinical trial NCT00405548: Human Brain Natriuretic Peptide (BNP) (or Nesiritide) to Help Heart, Kidney and Humoral Function.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Left Ventricular Diastolic Dysfunction
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Scios, Inc.
name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Research Resources (NCRR)
First posted: 2006-11-30
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Urinary Sodium Excretion in Response to Saline Load
timeFrame: Baseline, 12 weeks
Secondary outcomes:
measure: Change in Urinary Flow in Response to Saline Load
timeFrame: Baseline, 12 weeks
measure: Change in Glomerular Filtration Rate (GFR) in Response to Saline Load
timeFrame: Baseline, 12 weeks
measure: Left Ventricular (LV) Filling Pressure
timeFrame: Baseline, 12 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Horng H. Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.