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

Primary Purpose

Left Ventricular Diastolic Dysfunction

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

BNP (nesiritide)

Placebo

About this trial

This is an interventional basic science trial for Left Ventricular Diastolic Dysfunction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

BNP (nesiritide)

Placebo

Arm Description

BNP 10 micrograms/Kg twice per day given subcutaneously for 12 weeks

Saline solution given subcutaneously twice per day for 12 weeks (packaged to match active comparator)

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT00405548

First Posted

November 29, 2006

Last Updated

June 3, 2015

Sponsor

Mayo Clinic

Collaborators

National Institutes of Health (NIH), Scios, Inc., National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)

1. Study Identification

Unique Protocol Identification Number

NCT00405548

Brief Title

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

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

March 2008 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

Collaborators

National Institutes of Health (NIH), Scios, Inc., National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Left Ventricular Diastolic Dysfunction

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

41 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BNP (nesiritide)

Arm Type

Active Comparator

Arm Description

BNP 10 micrograms/Kg twice per day given subcutaneously for 12 weeks

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Saline solution given subcutaneously twice per day for 12 weeks (packaged to match active comparator)

Intervention Type

Drug

Intervention Name(s)

BNP (nesiritide)

Other Intervention Name(s)

natrecor, nesiritide

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Change in Urinary Sodium Excretion in Response to Saline Load

Description

Renal (or kidney) function was measured by the sodium or salt in the urine, following administration of a pre-specified amount of saline (salt).

Time Frame

Baseline, 12 weeks

Secondary Outcome Measure Information:

Title

Change in Urinary Flow in Response to Saline Load

Description

Urinary flow is a measure of renal (or kidney) function and was measured in milliliters per minute.

Time Frame

Baseline, 12 weeks

Title

Change in Glomerular Filtration Rate (GFR) in Response to Saline Load

Description

Time Frame

Baseline, 12 weeks

Title

Left Ventricular (LV) Filling Pressure

Description

Time Frame

Baseline, 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Horng H. Chen, M.D.

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

26874387

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.

Results Reference

derived

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

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