Left Ventricular Diastolic DysfunctionPhase 1/2NCT00405548
Human Brain Natriuretic Peptide (BNP) (or Nesiritide) to Help Heart, Kidney and Humoral Function.
A Phase 1/2 study testing BNP (nesiritide) in people with Left Ventricular Diastolic Dysfunction, run by Mayo Clinic at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Left Ventricular Diastolic Dysfunction
- What is being tested?
- BNP (nesiritide)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Aug 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Left Ventricular Diastolic Dysfunction
- Being tested
- BNP (nesiritide), Placebo
- Medical subject headings
- Ventricular Dysfunction, Left
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNP (nesiritide)Drug
Also called natrecor, nesiritide
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| BNP (nesiritide) | Active comparator | BNP 10 micrograms/Kg twice per day given subcutaneously for 12 weeks Receives: Drug: BNP (nesiritide) |
| Placebo | Placebo comparator | Saline solution given subcutaneously twice per day for 12 weeks (packaged to match active comparator) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline, 12 weeks
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Baseline, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2006 (estimated)
- Study startMar 2008
- Primary completionApr 2011
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Left Ventricular Diastolic DysfunctionStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Scios, Inc., National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, Horng Chen, Mayo Clinic
- Investigators
- Horng H. Chen, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00405548
- Sponsor's protocol ID
- 05-004190
- Other IDs
- P01HL076611, UL1RR024150
- Status last verified
- Jun 2015
- First submitted
- 29 Nov 2006
- Last updated
- 1 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 26874387
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00405548
- Acronym / sponsor ID
- 05-004190
- Conditions
- Left Ventricular Diastolic Dysfunction
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Scios, Inc., National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)
- Study start
- Mar 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 30 Nov 2006 (estimated)
- Results
- Posted 9 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BNP (nesiritide) | Active comparator | Drug: BNP (nesiritide)BNP 10 micrograms/Kg twice per day given subcutaneously for 12 weeks |
| Placebo | Placebo comparator | Drug: PlaceboSaline solution given subcutaneously twice per day for 12 weeks (packaged to match active comparator) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BNP (nesiritide)Also: natrecor, nesiritide | Drug | BNP (nesiritide) |
| Placebo | Drug | Placebo |
Primary outcome
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).
3 secondary outcomes
Change in Urinary Flow in Response to Saline Load
Time frame: Baseline, 12 weeks
Change in Glomerular Filtration Rate (GFR) in Response to Saline Load
Time frame: Baseline, 12 weeks
Left Ventricular (LV) Filling Pressure
Time frame: Baseline, 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26874387Wan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Horng H. Chen, M.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BNP (nesiritide) in people with Left Ventricular Diastolic Dysfunction, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Urinary Sodium Excretion in Response to Saline Load (time frame: Baseline, 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00405548, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2015.