Evaluation of Cardiac and Endothelial Function in Children and Adolescents Treated With Anthracycline

NCT ID: NCT07253077

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2027-01-31

Brief Summary

In recent decades, the survival rate of children with cancer has increased significantly thanks to personalized treatments and the adoption of international therapeutic protocols. However, along with this increase in survival, side effects related to these treatments on various organs and systems have been observed.

Among the most widely used chemotherapeutic agents in pediatric age, anthracyclines play a crucial role in the treatment of various forms of neoplasms (both haematological such as acute lymphoblastic leukemia or lymphomas, and solid tumors such as sarcomas). However, in addition to their excellent antineoplastic effect, they are burdened by the potential for cardiotoxicity. This cardiotoxicity manifests clinically with left ventricular systolic dysfunction and arrhythmias.

At the moment, international guidelines recommend long-term cardiac follow-up evaluations for this group of patients, even after treatment has concluded.The methods used in the cardiac follow-up of patients undergoing anthracycline therapy include echocardiography, cardiac magnetic resonance imaging, tests to assess endothelial function, and measurements of the biomarkers troponin and atrial natriuretic peptide. These methods can assess anthracycline-induced cardiac and endothelial damage once it has already occurred, but they cannot predict its onset nor can they study its pathogenesis.

Furthermore, to date, no information is available regarding the possibility of using "endothelial-mesenchymal transition" biomarkers as predictors of the onset of anthracycline-induced cardiac damage.

This study analyzes these biomarkers as predictive tools for cardiac damage. Specifically, plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, and endothelin will be measured in patients treated with anthracycline. The concentrations of these biomarkers will be compared with the results of the echocardiogram and with the treatments performed in order to identify any relationships. Furthermore, plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, and endothelin will also be measured in a population of healthy subjects in order to obtain data on a possible relationship between the biomarkers and the anthracycline therapies performed.

Conditions

Anthracycline Related Cardiotoxicity in Childhood Cancers; Chemotherapeutic Toxicity; Childhood Cancer Survivors

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: OTHER

Study Groups

Patients treated with anthracyclines

Patients who recovered from cancers and who underwent treatment with anthracyclines (from January 2010 to November 2024) and are undergoing regular follow-up. Inclusion criteria for the patient group:

• diagnosis of hematologic oncology during childhood (diagnosis made between 0 and 16 years of age);
• age at enrollment greater than or equal to 6 years;
• having received anthracycline chemotherapy;
• disease remission for at least 1 year;
• absence of known cardiac disease prior to anthracycline therapy;
• absence of congenital heart disease.

Biomarker detection

Intervention Type: DIAGNOSTIC_TEST

All patients will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin.

In addition, the study will collect the following anamnestic data:

• patient demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data;
• data relating to the neoplastic pathology and treatment performed

Control group

Subjects never treated with anthracyclines and free of cancer. Inclusion criteria for the control group:

• Age at enrollment greater than or equal to 6 years;
• Good health.

Biomarker detection

Intervention Type: DIAGNOSTIC_TEST

All controls will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin.

In addition, the study will collect information on demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data.

Interventions

Biomarker detection

All patients will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin.

In addition, the study will collect the following anamnestic data:

• patient demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data;
• data relating to the neoplastic pathology and treatment performed

Intervention Type: DIAGNOSTIC_TEST

Biomarker detection

All controls will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin.

In addition, the study will collect information on demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• diagnosis of cancer during childhood (diagnosis made between 0 and 16 years of age);
• age at enrollment greater than or equal to 6 years;
• having received anthracycline chemotherapy;
• disease remission for at least 1 year;
• absence of known cardiac disease prior to anthracycline therapy;
• absence of congenital heart disease.

• age at the time of enrollment: 6 years or older;
• good health.

Exclusion Criteria

• disease remission for less than 1 year;
• age less than 6 years at the time of enrollment;
• presence of known comorbidities (cardiopulmonary diseases, neurological diseases, etc.).

• having had oncological diseases;
• having undergone thoracic radiotherapy;
• having undergone anthracycline chemotherapy;
• being under 6 years of age at the time of enrollment;
• having known comorbidities (cardiopulmonary diseases, neurological diseases, etc.).

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Ruggiero

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Countries

Italy

Central Contacts

Antonio Ruggiero, MD

Role: CONTACT

antonio.ruggiero@unicatt.it

+39 0630158305

Facility Contacts

Antonio Ruggiero, MD

Role: primary

antonio.ruggiero@policlinicogemelli.it

+39 0630158305

Other Identifiers

7304

Identifier Type: -

Identifier Source: org_study_id