Neuregulin-1 in Patient With Different Forms of Cardiovascular Diseases: a Pilot Study

NCT04391491 | Completed DMC

• 1 other identifier: 03-19 13022019
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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). 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.

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

Outcome Measures

Primary Outcomes (1)

• 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)

  up to 3 days

Secondary Outcomes (1)

• Correlations between NRG-1 and NTproBNP, biomarkers of inflammation and fibrosis

  14 days

Study Arms (4)

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)

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)

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'

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))

Diagnostic Test: Neuregulin-1β level in plasma

Interventions

Neuregulin-1β level in plasma DIAGNOSTIC_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

Heart failure with preserved ejection fraction; Heart failure with redused ejection fraction; Microvascular angina; Pulmonary hypertension

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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))

You may not qualify if:

• 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
• Severe hepatic or renal dysfunction
• Severe nervous system diseases
• History of any malignancy or suffering from cancer
• Lack of informed consent

Sponsors & Collaborators

• I.M. Sechenov First Moscow State Medical University: lead
• Universiteit Antwerpen: collaborator
• University of Basel: collaborator

Study Sites (1)

Anastasia Shchendrygina

Moscow, 119415, Russia

Location

Related Publications (1)

• 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.

  PMID: 31607147 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples for analysis of neuregulin-1β, NT-proBNP, biomarkers of inflammation and fibrosis

MeSH Terms

Conditions

Microvascular Angina; Hypertension, Pulmonary; Fibromatosis, Gingival, 2

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension

Study Officials

• Anastasia Shchendrygina

  I.M. Sechenov First Moscow State Medical University (Sechenov University)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: May 18, 2020
• Study Start: March 1, 2019
• Primary Completion: December 1, 2022
• Study Completion: February 1, 2023
• Last Updated: May 3, 2023

Record last verified: 2021-09

Locations

RU (1)