Nesiritide in Hypertension (TENSE1)
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|ClinicalTrials.gov Identifier: NCT02608996|
Recruitment Status : Recruiting
First Posted : November 20, 2015
Last Update Posted : January 3, 2018
Hypertension remains a global burden in cardiovascular disease leading to stroke, myocardial infarction, and heart failure. Its myocardial complications result from increased mechanical load on the heart. Under physiological conditions of increased myocardial load and resulting myocardial stretch, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) synthesis and secretion occur contributing to maintenance of optimal cardiorenal and blood pressure homeostasis. However, studies indicate that in subjects with cardiovascular diseases the biological structure of these hormones may be altered, thus reducing their favorable protective activities. New studies indicate that early and moderate hypertension is associated with a derangement of the natriuretic peptide system which is characterized by the lack of activation of biologically active ANP and BNP, while severe hypertension is characterized by cardiac release of altered molecular forms of ANP and BNP that have reduced biological properties and/or enhanced degradation.
The broad objective of this proposal is to advance the biology and therapeutics of the NPs with a special focus on the cardiac peptide BNP in human hypertension. Our proposal is based upon the biological properties of BNP (i.e. natriuretic, renin-angiotensin-aldosterone suppressing, vasodilating, anti-fibrotic, anti-hypertrophic and positive lusitropic), its mechanistic role in human hypertension, and thus its potential as an innovative chronic protein therapeutic to enhance the treatment of patients with hypertension. Importantly, BNP is an endocrine hormone normally produced by the human heart, and it has been approved for the treatment of acute heart failure in USA.
|Condition or disease||Intervention/treatment||Phase|
|Hypertension||Drug: Nesiritide Drug: Placebo||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Therapeutic Effects of BNP in Hypertensive Patients|
|Study Start Date :||December 2015|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2030|
Active Comparator: Subcutaneous BNP
Patients will receive gradually increasing doses (10-25 µg/kg) of subcutaneously administered nesiritide (BNP) twice daily for two days, to determine the feasibility, safety and blood pressure lowering effect of BNP so as to identify the optimal dose.
This intervention is designed to determine the optimal dose range of BNP for treatment of patients with uncontrolled hypertension
Other Name: Natrecor, BNP
Placebo Comparator: Subcutaneous placebo
Patients will receive subcutaneously administered placebo twice daily for two days for determination of the effect of BNP.
For comparison to elucidate the true effect of nesiritide
Other Name: Saline solution
- Changes in blood pressure (BP) [ Time Frame: 48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection(baseline data) up to 12 hours post last injection. ]Office blood pressure and ambulatory blood pressure monitoring (ABPM) recordings will be used for the analysis
- Renal function as assessed by estimated glomerular filtration rate (eGFR) [ Time Frame: 48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection (baseline data) up to 12 hours post last injection. ]Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation will be used to calculate estimated glomerular filtration rate (eGFR).
- Hormonal changes assessed by aldosterone, atrial natriuretic peptide (ANP), N Terminal-ANP, BNP, N Terminal-proBNP, C-type natriuretic peptide and cyclic guanosyl monophosphate. [ Time Frame: 48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection (baseline data) up to 12 hours post last injection. ]Will be measured in plasma, and all but aldosterone in urine Collections.
- Number of participants with treatment-related adverse events defined as all untoward and unintended responses to the treatment related to any dose administered. [ Time Frame: 48 hours, from day 1 to day 2. Specifically, it will be assessed after first injection, up to 12 hours post last injection. A second determination will be done within 3 weeks after last injection (21 days assessment). ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02608996
|Contact: Alessandro Cataliotti, MD, PhD||+47 firstname.lastname@example.org|
|Oslo University Hopital, Rikshospitalet||Not yet recruiting|
|Oslo, Norway, 0424|
|Contact: Hassan Z Khiabani, MD, PhD|
|Sub-Investigator: Hassan Z Khiabani, MD, PhD|
|Oslo University Hospital, Ullevål Hospital||Recruiting|
|Oslo, Norway, 0450|
|Contact: Morten Rostrup, MD, PhD|
|Sub-Investigator: Kaja K Bergo, MD|
|Sub-Investigator: Morten Rostrup, MD, PhD|
|Sub-Investigator: Einar S Norden|
|Sub-Investigator: Ivar Sjaastad, MD, PhD|
|Akershus University Hospital||Recruiting|
|Strømmen, Norway, 1478|
|Contact: My HS Svensson, MD, PhD|
|Sub-Investigator: My HS Svensson, MD, PhD|
|Sub-Investigator: Helge Røsjø, MD, PhD|
|Principal Investigator:||Alessandro Cataliotti, MD, PhD||Oslo University Hospital and University of Oslo|