Biomarkers of CVD Dysfunction in Hypertensive Disorders of Pregnancy

Cardiovascular Diseases Clinical Trial

Official title:

Biomarkers of Maternal Cardio-vascular Dysfunction in Pregnancies Complicated by Hypertensive Disorders of Pregnancy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05806372
• Other study ID #: RC 29/22
• Status: Not yet recruiting
• Start date: October 15, 2023
• Est. completion date: March 15, 2025

Study information

• Verified date: August 2023
• Source: IRCCS Burlo Garofolo
• Contact: Tamara Stampalija, MD
• Phone: +390403785486
• Email: tamara.stampalija[@]burlo.trieste.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Profound and concomitant cardiovascular hemodynamic changes, necessary to support fetoplacental development and its increasing supply demands, occur during a physiological pregnancy characterized by an increase in cardiac output, heart rate and plasma volume, and fall in vascular resistance and blood pressure. The result of these changes is a volume overload that will lead to a compensatory transient left ventricular eccentric hypertrophy. This, together with the pro-inflammatory state typical of pregnancy, represents the pregnancy as a stress-test for the maternal cardiovascular system. Pregnancies complicated by hypertensive disorders of pregnancy (HDP), particularly those with early onset and/or complicated by intrauterine fetal growth restriction (FGR), are characterized by a cardiovascular maladaptation. Women who experienced HDP in pregnancy, especially pre-eclampsia (PE), more often develop later in life ischemic heart disease, hypertension and stroke, obesity, dyslipidemia, and end-stage renal disease.

Regardless its clinical impact, very little knowledge is available on the mechanisms by which PE could lead to cardiovascular disease (CVD), and, especially, to heart failure after pregnancy. Preliminary results suggest a cross-talk between pregnancy-induced biomarkers and cardio-vascular system. Particularly, cultures of neonatal rat cardiomyocytes and fibroblasts were used to investigate the role of the serum of women with HDP in regulating their proliferation. 5-ethynyl-2'-deoxyuridine (EdU) was administered to label DNA synthesis in proliferating cells. After 3 days of in vitro culture, EdU incorporation was analyzed upon immunofluorescence staining using specific antibodies by high content microscopy. A possible protective effect exerted by the selected sera against apoptosis was evaluated, as well, by Caspase activation. Moreover, the effect of cardiomyocytes and fibroblasts proliferation and apoptosis on maternal hemodynamic parameters was evaluated using median regression models. These data show that the serum of women with HDP triggers a net increase in the percentage of proliferating cardiomyocytes compared to controls. Moreover, there were relationship between cardiomyocytes and fibroblasts proliferation and maternal hemodynamics parameters thus, supporting the hypothesis that the serum of women with HDP may contain factors capable of stimulating cardiac cells in response to the cardiovascular stress-test

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 128
• Est. completion date: March 15, 2025
• Est. primary completion date: March 15, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

CASES:

1. Pregnant women affected by HDP

2. Women =18 years old

3. Women able to give an informed consent

CONTROLS

1. Uneventful pregnancy of women =18 years old

2. Women able to give an informed consent

Exclusion Criteria:

1. No informed consent

2. Women <18 years old

3. Presence of other maternal pathologies as viral disease, diabetes

4. Fetal chromosomal/structural anomalies

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Hypertension
• Pre-Eclampsia
• Pregnancy
• Toxemia

Locations

Country	Name	City	State
Italy	IRCCS Burlo Garofolo	Trieste

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Burlo Garofolo

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of biomarkers predicting cardiomyocyte hypertrophy and fibroblast proliferation	By exploiting the availability of a library of viral vectors encoding for the whole secretome (about 1200 secreted proteins) and the whole miRNAome (about 2000 human microRNAs) a high throughput screening will be carried out to identify molecules able to control the viability, proliferation and cell size of both primary cardiomyocytes and cardiac fibroblasts. Data mining methods for multi-target prediction, such as ensembles of predictive clustering trees, will be used to correlate multiple independent variables (e.g., potential biomarkers) to the multiple clinical outcomes (indices of cardio-vascular dysfunction measured by echocardiography).	During pregnancy, at the time of HDP diagnosis
Primary	Number of biomarkers predicting cardiomyocyte hypertrophy and fibroblast proliferation	By exploiting the availability of a library of viral vectors encoding for the whole secretome (about 1200 secreted proteins) and the whole miRNAome (about 2000 human microRNAs) a high throughput screening will be carried out to identify molecules able to control the viability, proliferation and cell size of both primary cardiomyocytes and cardiac fibroblasts. Data mining methods for multi-target prediction, such as ensembles of predictive clustering trees, will be used to correlate multiple independent variables (e.g., potential biomarkers) to the multiple clinical outcomes (indices of cardio-vascular dysfunction measured by echocardiography).	24 months post-partum