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

Last updated: May 2, 2023
Sponsor: I.M. Sechenov First Moscow State Medical University
Overall Status: Completed

Phase

N/A

Condition

Hyponatremia

Williams Syndrome

Angina

Treatment

Neuregulin-1β level in plasma

Clinical Study ID

NCT04391491
03-19 13022019
  • Ages 18-75
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Able to provide informed consent
  • Confirmed diagnosis of HFpEF (Symptoms of HF (NYHA II-IV); LVEF >50%; Elevated levelsof natriuretic peptides (NT-pro BNP > 300 pg/ml in sinus rhythm, >600 pg/ml inAF);Relevant structural heart disease (Left ventricle hypertrophy (LVH) and/or Leftatrium enlargement (LAE); left atrial volume index (LAVI) >34 mL/m2 or a leftventricular 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-segmentdepression in >2 leads)); No fixed stenosis (>50%) in epicardial coronary arteries orbranches at baseline coronary arteriography)
  • Confirmed diagnosis of PH (PH due to left heart disease (Left ventricular systolicdysfunction, Left ventricular diastolic dysfunction, Valvular disease,Congenital/acquired left heart inflow/outflow obstruction and congenitalcardiomyopathies); Chronic thromboembolic pulmonary hypertension; Peak tricuspidregurgitation velocity =2.8 m/s and presence of other echo 'PH signs')
  • Confirmed diagnosis of HFrEF (Symptomatic HF (NYHA class II-IV), left ventricularejection fraction ≤ 35% (at any time in the past))

Exclusion

Exclusion Criteria:

  • Patients with hypertrophic cardiomyopathy, rheumatic heart disease, constrictivepericarditis, 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 (symptomsand signs suggest worsening chronic heart failure and may require intravenous drugtherapy)
  • 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 Design

Total Participants: 100
Treatment Group(s): 1
Primary Treatment: Neuregulin-1β level in plasma
Phase:
Study Start date:
March 01, 2019
Estimated Completion Date:
February 01, 2023

Study 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.

Connect with a study center

  • Anastasia Shchendrygina

    Moscow, 119415
    Russian Federation

    Site Not Available

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