Human B-type Natriuretic Peptide (BNP) (Nesiritide) to Help Heart, Kidney, and Hormonal Functions in Persons With Lower Heart Pumping Function

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Horng Chen, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00405639
First received: November 29, 2006
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

The following are done for screening procedures to determine if patients are eligible for this study: blood count, kidney and liver blood tests. Patients will complete a 6-minute walk test. Patients will be instructed to follow a no-added-salt diet for 1-3 weeks before the study and for the whole duration of the study. Diet instructions will be given to the patient and the patient will collect his/her urine for 24 hours before the active study day. Patients will need to avoid strenuous exercise and abstain from smoking, alcohol, and caffeine for 3 days prior to the study days. Patients will remain on their regular medications.


Condition Intervention Phase
Heart Failure
Asymptomatic Systolic Dysfunction
Drug: Nesiritide
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: To Define in Human Preclinical Systolic Dysfunction (PSD) 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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in Urinary Sodium Excretion in Response to Saline Load [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Urine Flow in Response to Saline Load [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
  • Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) in Response to Saline Load [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    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/min/1.73 m^2 of body surface area is considered to be impaired kidney function.

  • Change in Left Ventricular Mass Index [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    Left ventricular mass index (LVMI) is a surrogate of left ventricular hypertrophy and a predictor of cardiac morbidity and mortality in adults with hypertension. LVMI was measured with echocardiography, indexed to body surface area estimated by left ventricular (LV) cavity dimension and wall thickness at end-diastole.


Enrollment: 37
Study Start Date: June 2006
Study Completion Date: May 2013
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nesiritide
Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is >90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Drug: Nesiritide
Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is >90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Other Names:
  • Natrecor
  • Human B-type natriuretic peptide (BNP)
Placebo Comparator: Placebo
Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Drug: Placebo
Normal saline will be used for placebo.

Detailed Description:

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 General Clinical Research Center (GCRC) at St. Marys Hospital. During the two in-patient stays in the GCRC, blood and urine samples will be done to get heart and kidney function as well as a research echo. After enrollment, the study lasts for twelve weeks. There is a one week visit in outpatient setting getting a blood draw and a 6 week visit in outpatient setting to get a blood draw, 24 hour urine collection and resupply the study medication. There is a one week visit in outpatient setting getting a blood draw and a 6 week visit in outpatient setting to get a blood draw, 24 hour urine collection and resupply the study medication.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects with an ejection fraction of less than 45%
  • No clinical signs or symptoms of congestive heart failure
  • Ability to walk a minimal distance of > 450 meters on a 6-minute walk. If the subject is not able to walk 450 meters due to pain in hips and knees and not fatigue or shortness of breath, they will still qualify for the protocol.
  • The subjects will all be on stable doses of an angiotensin converting enzyme (ACE) inhibitor for two weeks prior to the active study date.
  • Therapy with other vasodilators, beta-receptor antagonists, digoxin and antiarrhythmic medications will be allowed, however, all medications must be at stable doses two weeks prior to the study date.

Exclusion criteria:

  • Myocardial infarction 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
  • Serum creatinine of > 3.0 mg/dL
  • Serum sodium of < 125 milliequivalent (mEq)/dL or > 160 mEq/dL
  • Serum potassium of < 3.5 mEq/dL or > 5.0 mEq/dL change to 5.3
  • Serum digoxin level of > 2.0 ng/ml
  • Systolic pressure of < 85 mmHg
  • Hemoglobin < 10 gm/dl
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405639

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Horng H. Chen, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Horng Chen, Dr Horng H. Chen, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00405639     History of Changes
Other Study ID Numbers: 05-004186, P01HL076611, UL1RR024150
Study First Received: November 29, 2006
Results First Received: February 4, 2014
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Natriuretic Peptide, Brain
Cardiovascular Agents
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014