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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
Sponsor:
Collaborators:
University of Oslo
University Hospital, Akershus
Information provided by (Responsible Party):
Alessandro Cataliotti, Oslo University Hospital

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Drug Information available for: Nesiritide

Arm Intervention/treatment
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.
Drug: Nesiritide
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.
Drug: Placebo
For comparison to elucidate the true effect of nesiritide
Other Name: Saline solution




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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). ]


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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Office systolic blood pressure (SBP) ≥ 120 mmHg and treatment with at least one anti-hypertensive medication. Unchanged medication regimen the last two weeks prior to inclusion.
  • Average day-time SBP > 115 on a 24-h ambulatory BP measurement at screening.

Exclusion Criteria:

  • Congestive Heart Failure (any New York Heart Association class)
  • Ejection Fraction ≤ 40 %
  • Known, not appropriately treated, secondary hypertension
  • Myocardial infarction within 3 months of screening
  • Unstable angina within 14 days of screening, or any evidence of myocardial ischemia
  • Pulmonary hypertension
  • Aortic stenosis with maximum jet velocity > 2,5 m/s
  • Other valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis or biopsy proven active myocarditis
  • Sustained Ventricular Tachycardia or Ventricular Fibrillation within 14 days of screening
  • Sustained Atrial Fibrillation
  • Second or third degree atrioventricular block without a permanent cardiac pacemaker
  • Cerebrovascular event within 3 months of screening, or other evidence of significantly compromised cerebral perfusion
  • Proteinuria defined as albumin:creatinine ratio > 100 (equivalent to an excretion of > 1 g/day)
  • Nephrotic syndrome
  • Body Mass Index > 35
  • Total bilirubin of > 25 µmol/L, aspartate aminotransferase or alanine aminotransferase 1.5 times the upper limit of normal range
  • Renal insufficiency assessed by estimated glomerular filtration rate (GFR) < 30 ml/min
  • Serum sodium of ≤ 135 mmol/L and ≥ 150 mmol/L
  • Serum potassium of ≤ 3.5 mmol/L and ≥ 5.5 mmol/L
  • Women taking hormonal contraceptives containing estrogens
  • Pregnancy
  • Patients on prolonged, i.e. more than 30 days, immunosuppressant therapy
  • Patients with known, active malignancies
  • Patients with orthostatic hypotension
  • Participation in a trial with an investigational product within the previous three months
  • Any contraindication listed on the Investigator's Brochure of the Investigational Medicinal Product
  • Any reason why, in the opinion of the investigator, the patient should not participate.

Information from the National Library of Medicine

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


Contacts
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Contact: Alessandro Cataliotti, MD, PhD +47 23016807 alessandro.cataliotti@medisin.uio.no

Locations
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Norway
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         
Sponsors and Collaborators
Oslo University Hospital
University of Oslo
University Hospital, Akershus
Investigators
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Principal Investigator: Alessandro Cataliotti, MD, PhD Oslo University Hospital and University of Oslo

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Responsible Party: Alessandro Cataliotti, Professor, dr. med., Oslo University Hospital
ClinicalTrials.gov Identifier: NCT02608996     History of Changes
Other Study ID Numbers: 2015-000577-13
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: January 3, 2018
Last Verified: December 2017

Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs