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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Mayo Clinic
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Change in Urinary Sodium Excretion in Response to Saline Load
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
BNP (nesiritide)
BNP 10 micrograms/Kg twice per day given subcutaneously for 12 weeks
Intervention: BNP (nesiritide) (Drug)
Placebo
Saline solution given subcutaneously twice per day for 12 weeks (packaged to match active comparator)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in Urinary Sodium Excretion in Response to Saline Load
Time Frame: 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 Outcomes
- Change in Urinary Flow in Response to Saline Load(Baseline, 12 weeks)
- Change in Glomerular Filtration Rate (GFR) in Response to Saline Load(Baseline, 12 weeks)
- Left Ventricular (LV) Filling Pressure(Baseline, 12 weeks)
Investigators
Horng Chen
Dr Horng H Chen
Mayo Clinic