Neuregulin-1 in Patient With Different Forms of Cardiovascular Diseases: a Pilot Study (NRG-1-CVDs)

May 2, 2023 updated by: I.M. Sechenov First Moscow State Medical University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

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

Description

Inclusion Criteria:

  • 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))

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
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
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
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
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
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 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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
up to 3 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlations between NRG-1 and NTproBNP, biomarkers of inflammation and fibrosis
Time Frame: 14 days
Correlations between NRG-1 and NTproBNP, biomarkers of inflammation and fibrosis will be assessed with suitable correlation analyses depending on normality of distribution
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

I.M. Sechenov First Moscow State Medical University

Collaborators

University of Basel
Universiteit Antwerpen

Investigators

  • Principal Investigator: Anastasia Shchendrygina, I.M. Sechenov First Moscow State Medical University (Sechenov University)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2019

Primary Completion (Actual)

December 1, 2022

Study Completion (Actual)

February 1, 2023

Study Registration Dates

First Submitted

May 13, 2020

First Submitted That Met QC Criteria

May 15, 2020

First Posted (Actual)

May 18, 2020

Study Record Updates

Last Update Posted (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

May 2, 2023

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-19 13022019

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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