Heart Failure With Preserved Ejection FractionNRG-1-CVDsNCT04391491
Neuregulin-1 in Patient With Different Forms of Cardiovascular Diseases: a Pilot Study
An observational study of Heart Failure With Preserved Ejection Fraction and Microvascular Angina, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
Trial summary
This is an observational study of Neuregulin-1 (NRG-1) plasma levels in patients with different forms of cardiovascular disease including microvascular angina (MVA), heart failure with preserved ejection fraction (HFpEF), as well as, heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH). Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Microvascular Angina, Pulmonary Hypertension
- What is being tested?
- Neuregulin-1β level in plasma
- Type of treatment
- Injection or infusion
- How many people
- 100 participants
- Where
- 1 siteRussia
- Study dates
- 1 Mar 2019to 1 Feb 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with a confirmed diagnosis of pulmonary hypertension, microvascular angina, heart failure with preserved ejection fraction or heart failure with reduced ejection fraction as defined by the diagnostic criteria in respective ESC guidelines
Who may be able to join
- Able to provide informed consent
- Confirmed diagnosis of HFpEF (Symptoms of HF (NYHA II-IV); LVEF >50%; Elevated levels of natriuretic peptides (NT-pro BNP > 300 pg/ml in sinus rhythm, >600 pg/ml in AF);Relevant structural heart disease (Left ventricle hypertrophy (LVH) and/or Left atrium enlargement (LAE); left atrial volume index (LAVI) >34 mL/m2 or a left ventricular mass index (LVMI) =115 g/m2 for males and =95 g/m2 for females)
- Confirmed diagnosis of MVA (Angina-like chest pain: signs of exercise-induced ischemia (ST-depression on exercise ECG (>1 mm down-sloping or rectilinear ST-segment depression in >2 leads)); No fixed stenosis (>50%) in epicardial coronary arteries or branches at baseline coronary arteriography)
- Confirmed diagnosis of PH (PH due to left heart disease (Left ventricular systolic dysfunction, Left ventricular diastolic dysfunction, Valvular disease, Congenital/acquired left heart inflow/outflow obstruction and congenital cardiomyopathies); Chronic thromboembolic pulmonary hypertension; Peak tricuspid regurgitation velocity =2.8 m/s and presence of other echo 'PH signs')
- Confirmed diagnosis of HFrEF (Symptomatic HF (NYHA class II-IV), left ventricular ejection fraction ≤ 35% (at any time in the past))
Who cannot join
- Patients with hypertrophic cardiomyopathy, rheumatic heart disease, constrictive pericarditis, significant valvular pathological change or congenital heart diseases
- Primary pulmonary artery hypertension
- Acute MI in the last 3 months
- Unstable angina
- Chronic heart failure patients with acute decompensation in the last 1 month (symptoms and signs suggest worsening chronic heart failure and may require intravenous drug therapy)
- Cardiac surgery or cerebrovascular accident within the recent six months
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- Severe hepatic or renal dysfunction
- Severe nervous system diseases
- History of any malignancy or suffering from cancer
- Lack of informed consent
Trial locations and contacts
1 site in 1 country.
About this study
This is an observational study of Neuregulin-1 (NRG-1) plasma levels in patients with different forms of cardiovascular disease including microvascular angina (MVA), heart failure with preserved ejection fraction (HFpEF), as well as, heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH). Investigators intend to identify cardiovascular diseases which are characterized by increased circulating NRG-1, considered to be a biomarker of therapeutic potential of NRG-1. Participants will undergo blood sampling over 3 days following randomisation. Patients demographics and clinical characteristics will be recorded and their associations with NRG-1 will be analysed.
Read the detailed description
NRG-1 is a paracrine growth factor with physiological actions in the cardiovascular system which is primarily expressed by the endothelium of coronary microvessels. NRG-1 is a natural paracrine agonist of the ErbB4 receptor. The NRG-1/ErbB4 system is activated in chronic heart failure (HF) and some other chronic diseases, exerting disease mitigation and regenerative effects. Recombinant NRG-1 (rhNRG-1) is developed as a drug for HFrEF. Both the preclinical and clinical data (phase II and III clinical trials) have demonstrated the favourable effects of NRG-1 treatment on the heart. rhNRG-1 effectively enhances the heart function and reverses the remodelling of the left ventricle. The levels of circulating NRG-1 were found to correlate with outcomes in Stage III and IV CHF. NRG1 appeared to be potentially protective Therefore, NRG-1 concentrations are considered to be a biomarker of the therapeutic potential of NRG-1. However, little is known about the role of the NRG-1 pathway in other cardiovascular diseases (CVDs). This observational study is intended to identify CVDs which are characterized by an increase in NRG-1 levels for better positioning the NRG-1 treatment in heterogeneous field of CVDs. Based on preclinical data, investigators assume that plasma NRG-1 will be altered in patients with microvascular angina, pulmonary hypertension, and HFpEF and HFrEF.
The study intends to enroll twenty patients for each of the 4 study groups and 20 healthy controls. We will compare the NRG-1 protein levels in patients and of age-matched healthy subjects. Participants will undergo a blood sampling after randomization (+ 3 days) and a 12 month follow up to assess the outcomes. Demographics, clinical characteristics, laboratory values including biomarkers of inflammation and fibrosis, NTproBNP, along with transthoracic echo findings and outcomes will be recorded. After the active phase of the research is done, we are planning to proceed to observation of the prospective group of patients to verify the endpoints.
- Conditions
- Heart Failure With Preserved Ejection Fraction, Microvascular Angina, Pulmonary Hypertension, Heart Failure With Reduced Ejection Fraction
- Being tested
- Neuregulin-1β level in plasma
- Keywords
- Neuregulin-1, Microvascular Angina,Heart Failure,Pulmonary Hypertension
- Medical subject headings
- Microvascular Angina, Hypertension, Pulmonary, Fibromatosis, Gingival, 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neuregulin-1β level in plasmaDiagnostic test
Peripheral blood will be collected after randomization (plus or minus 3 days), the plasma will be assayed for neuregulin-1b, biomarkers of inflammation and fibrosis, NTproBNP
| Study group | Role | What they receive |
|---|---|---|
| Heart failure with preserved ejection fraction | Patients of both sexes and > 18 years with a confirmed diagnosis of HFpEF (Symptoms of HF (NYHA II-IV); LVEF >50%; Elevated levels of natriuretic peptides (NT-pro BNP > 300 pg/ml in sinus rhythm, >600 pg/ml in AF);Relevant structural heart disease (Left ventricle hypertrophy (LVH) and/or Left atrium enlargement (LAE); left atrial volume index (LAVI) >34 mL/m2 or a left ventricular mass index (LVMI) =115 g/m2 for males and =95 g/m2 for females) Receives: Diagnostic Test: Neuregulin-1β level in plasma | |
| Microvascular angina | Patients of both sexes and > 18 years with a confirmed diagnosis of MVA (Angina-like chest pain: signs of exercise-induced ischemia (ST-depression on exercise ECG (>1 mm down-sloping or rectilinear ST-segment depression in >2 leads)); No fixed stenosis (>50%) in epicardial coronary arteries or branches at baseline coronary arteriography) Receives: Diagnostic Test: Neuregulin-1β level in plasma | |
| Pulmonary hypertension | Patients of both sexes and > 18 years with a confirmed diagnosis of secondary PH due to left heart disease (Left ventricular systolic dysfunction, left ventricular diastolic dysfunction, Valvular disease, Congenital/acquired left heart inflow/outflow obstruction and congenital cardiomyopathies) or chronic thromboembolic pulmonary hypertension defined by echo when peak tricuspid regurgitation velocity =2.8 m/s and presence of other echo 'PH signs' Receives: Diagnostic Test: Neuregulin-1β level in plasma | |
| Heart failure with redused ejection fraction | Patients of both sexes and > 18 years with a confirmed diagnosis of HFrEF (Symptomatic HF (NYHA class II-IV), left ventricular ejection fraction ≤ 35% (at any time in the past)) Receives: Diagnostic Test: Neuregulin-1β level in plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
NRG-1 plasma concentrations
Peripheral blood will be collected after randomization (plus or minus 3 days) in vacuum tubes containing EDTA. Blood samples will be centrifugated within 30 minutes of collection. Then plasma will be separated and procced for NRG-1 measurement using the R\&D ELISA (R\&D cat# DY377)
Measured: up to 3 days
Secondary outcomes (1)
Correlations between NRG-1 and NTproBNP, biomarkers of inflammation and fibrosis
Correlations between NRG-1 and NTproBNP, biomarkers of inflammation and fibrosis will be assessed with suitable correlation analyses depending on normality of distribution
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2020
- Study start1 Mar 2019
- Primary completion1 Dec 2022
- Study completion1 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- I.M. Sechenov First Moscow State Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Universiteit Antwerpen, University of Basel
- Responsible party
- Sponsor
- Investigators
- Anastasia Shchendrygina, Principal investigator, I.M. Sechenov First Moscow State Medical University (Sechenov University)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04391491
- Sponsor's protocol ID
- 03-19 13022019
- Acronym
- NRG-1-CVDs
- Status last verified
- Sep 2021
- First submitted
- 13 May 2020
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
De Keulenaer GW, Feyen E, Dugaucquier L, Shakeri H, Shchendrygina A, Belenkov YN, Brink M, Vermeulen Z, Segers VFM. Mechanisms of the Multitasking Endothelial Protein NRG-1 as a Compensatory Factor During Chronic Heart Failure. Circ Heart Fail. 2019 Oct;12(10):e006288. doi: 10.1161/CIRCHEARTFAILURE.119.006288. Epub 2019 Oct 14.
PubMed 31607147
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuregulin-1 in Patient With Different Forms of Cardiovascular Diseases: a Pilot Study
- ClinicalTrials.gov ID
- NCT04391491
- Acronym / sponsor ID
- NRG-1-CVDs / 03-19 13022019
- Conditions
- Heart Failure With Preserved Ejection Fraction, Microvascular Angina, Pulmonary Hypertension, Heart Failure With Reduced Ejection Fraction
- Keywords
- Neuregulin-1, Microvascular Angina,Heart Failure,Pulmonary Hypertension
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- I.M. Sechenov First Moscow State Medical UniversityUniversity, hospital or other
- Collaborators
- Universiteit Antwerpen, University of Basel
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 1 Feb 2023 (actual)
- First posted
- 18 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an observational study of Neuregulin-1 (NRG-1) plasma levels in patients with different forms of cardiovascular disease including microvascular angina (MVA), heart failure with preserved ejection fraction (HFpEF), as well as, heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH). Investigators intend to identify cardiovascular diseases which are characterized by increased circulating NRG-1, considered to be a biomarker of therapeutic potential of NRG-1. Participants will undergo blood sampling over 3 days following randomisation. Patients demographics and clinical characteristics will be recorded and their associations with NRG-1 will be analysed.
Detailed description
NRG-1 is a paracrine growth factor with physiological actions in the cardiovascular system which is primarily expressed by the endothelium of coronary microvessels. NRG-1 is a natural paracrine agonist of the ErbB4 receptor. The NRG-1/ErbB4 system is activated in chronic heart failure (HF) and some other chronic diseases, exerting disease mitigation and regenerative effects. Recombinant NRG-1 (rhNRG-1) is developed as a drug for HFrEF. Both the preclinical and clinical data (phase II and III clinical trials) have demonstrated the favourable effects of NRG-1 treatment on the heart. rhNRG-1 effectively enhances the heart function and reverses the remodelling of the left ventricle. The levels of circulating NRG-1 were found to correlate with outcomes in Stage III and IV CHF. NRG1 appeared to be potentially protective Therefore, NRG-1 concentrations are considered to be a biomarker of the therapeutic potential of NRG-1. However, little is known about the role of the NRG-1 pathway in other cardiovascular diseases (CVDs). This observational study is intended to identify CVDs which are characterized by an increase in NRG-1 levels for better positioning the NRG-1 treatment in heterogeneous field of CVDs. Based on preclinical data, investigators assume that plasma NRG-1 will be altered in patients with microvascular angina, pulmonary hypertension, and HFpEF and HFrEF.
The study intends to enroll twenty patients for each of the 4 study groups and 20 healthy controls. We will compare the NRG-1 protein levels in patients and of age-matched healthy subjects. Participants will undergo a blood sampling after randomization (+ 3 days) and a 12 month follow up to assess the outcomes. Demographics, clinical characteristics, laboratory values including biomarkers of inflammation and fibrosis, NTproBNP, along with transthoracic echo findings and outcomes will be recorded. After the active phase of the research is done, we are planning to proceed to observation of the prospective group of patients to verify the endpoints.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Heart failure with preserved ejection fraction | – | Diagnostic Test: Neuregulin-1β level in plasmaPatients of both sexes and > 18 years with a confirmed diagnosis of HFpEF (Symptoms of HF (NYHA II-IV); LVEF >50%; Elevated levels of natriuretic peptides (NT-pro BNP > 300 pg/ml in sinus rhythm, >600 pg/ml in AF);Relevant structural heart disease (Left ventricle hypertrophy (LVH) and/or Left atrium enlargement (LAE); left atrial volume index (LAVI) >34 mL/m2 or a left ventricular mass index (LVMI) =115 g/m2 for males and =95 g/m2 for females) |
| Microvascular angina | – | Diagnostic Test: Neuregulin-1β level in plasmaPatients of both sexes and > 18 years with a confirmed diagnosis of MVA (Angina-like chest pain: signs of exercise-induced ischemia (ST-depression on exercise ECG (>1 mm down-sloping or rectilinear ST-segment depression in >2 leads)); No fixed stenosis (>50%) in epicardial coronary arteries or branches at baseline coronary arteriography) |
| Pulmonary hypertension | – | Diagnostic Test: Neuregulin-1β level in plasmaPatients of both sexes and > 18 years with a confirmed diagnosis of secondary PH due to left heart disease (Left ventricular systolic dysfunction, left ventricular diastolic dysfunction, Valvular disease, Congenital/acquired left heart inflow/outflow obstruction and congenital cardiomyopathies) or chronic thromboembolic pulmonary hypertension defined by echo when peak tricuspid regurgitation velocity =2.8 m/s and presence of other echo 'PH signs' |
| Heart failure with redused ejection fraction | – | Diagnostic Test: Neuregulin-1β level in plasmaPatients of both sexes and > 18 years with a confirmed diagnosis of HFrEF (Symptomatic HF (NYHA class II-IV), left ventricular ejection fraction ≤ 35% (at any time in the past)) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a confirmed diagnosis of pulmonary hypertension, microvascular angina, heart failure with preserved ejection fraction or heart failure with reduced ejection fraction as defined by the diagnostic criteria in respective ESC guidelines
Key inclusion criteria (5 listed)
- Able to provide informed consent
- Confirmed diagnosis of HFpEF (Symptoms of HF (NYHA II-IV); LVEF >50%; Elevated levels of natriuretic peptides (NT-pro BNP > 300 pg/ml in sinus rhythm, >600 pg/ml in AF);Relevant structural heart disease (Left ventricle hypertrophy (LVH) and/or Left atrium enlargement (LAE); left atrial volume index (LAVI) >34 mL/m2 or a left ventricular mass index (LVMI) =115 g/m2 for males and =95 g/m2 for females)
- Confirmed diagnosis of MVA (Angina-like chest pain: signs of exercise-induced ischemia (ST-depression on exercise ECG (>1 mm down-sloping or rectilinear ST-segment depression in >2 leads)); No fixed stenosis (>50%) in epicardial coronary arteries or branches at baseline coronary arteriography)
- Confirmed diagnosis of PH (PH due to left heart disease (Left ventricular systolic dysfunction, Left ventricular diastolic dysfunction, Valvular disease, Congenital/acquired left heart inflow/outflow obstruction and congenital cardiomyopathies); Chronic thromboembolic pulmonary hypertension; Peak tricuspid regurgitation velocity =2.8 m/s and presence of other echo 'PH signs')
- Confirmed diagnosis of HFrEF (Symptomatic HF (NYHA class II-IV), left ventricular ejection fraction ≤ 35% (at any time in the past))
Key exclusion criteria (10 listed)
- Patients with hypertrophic cardiomyopathy, rheumatic heart disease, constrictive pericarditis, significant valvular pathological change or congenital heart diseases
- Primary pulmonary artery hypertension
- Acute MI in the last 3 months
- Unstable angina
- Chronic heart failure patients with acute decompensation in the last 1 month (symptoms and signs suggest worsening chronic heart failure and may require intravenous drug therapy)
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 |
|---|---|---|
| Neuregulin-1β level in plasmaPeripheral blood will be collected after randomization (plus or minus 3 days), the plasma will be assayed for neuregulin-1b, biomarkers of inflammation and fibrosis, NTproBNP | Diagnostic test | Heart failure with preserved ejection fraction, Heart failure with redused ejection fraction, Microvascular angina, Pulmonary hypertension |
Primary outcome
NRG-1 plasma concentrations
Time frame: up to 3 days
Peripheral blood will be collected after randomization (plus or minus 3 days) in vacuum tubes containing EDTA. Blood samples will be centrifugated within 30 minutes of collection. Then plasma will be separated and procced for NRG-1 measurement using the R\&D ELISA (R\&D cat# DY377)
1 secondary outcome
Correlations between NRG-1 and NTproBNP, biomarkers of inflammation and fibrosis
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Background: PubMed 31607147De Keulenaer GW, Feyen E, Dugaucquier L, Shakeri H, Shchendrygina A, Belenkov YN, Brink M, Vermeulen Z, Segers VFM. Mechanisms of the Multitasking Endothelial Protein NRG-1 as a Compensatory Factor During Chronic Heart Failure. Circ Heart Fail. 2019 Oct;12(10):e006288. doi: 10.1161/CIRCHEARTFAILURE.119.006288. Epub 2019 Oct 14.
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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.
Anastasia Shchendrygina principal investigator
I.M. Sechenov First Moscow State Medical University (Sechenov University)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure With Preserved Ejection Fraction and Microvascular Angina, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
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 5 inclusion and 10 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 3 May 2023. 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 Russia. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
NRG-1 plasma concentrations (time frame: up to 3 days). 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 NCT04391491, 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 3 May 2023.