Late Anthracycline Induced Cardiotoxicity- Childhood Cancer Survivors

Sponsor

Queen's University, Belfast (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04852965

Collaborator

(none)

208

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Anthracyclines treat up to 60% of childhood malignancies with remarkable improvements survival rates. Unfortunately anthracyclines are associated with an increased cardiomyopathy risk. One study showed an almost six-fold greater risk of developing cardiomyopathy compared to sibling controls. A retrospective pilot study showed evidence of subclinical dysfunction (including impaired global longitudinal strain) in 42/52 childhood cancer survivors. There is limited research in this area, therefore current guidelines are based on expert opinion alone and lack consensus. Current methods of detection diagnose cardiomyopathy at an irreversible stage i.e. when the compensatory mechanisms are exhausted and the left ventricular ejection fraction impaired. Small trials have shown that early treatment with standard heart failure therapy may reverse damage, further validation is however required in this cohort.

Newer techniques such as tissue doppler and strain rate imaging have shown promise for early prediction of cardiomyopathy in adult studies. Biomarkers such as troponin and NT-proBNP have also shown a correlation with cardiomyopathy.

This study (n=208) aims to use echocardiography, strain imaging, holter monitoring and MRI for early detection of cardiomyopathy. Biomarkers, both currently used (for example, troponin and NTproBNP,) and more novel (for example, IL6, MPO, and sST2) will be assessed to see if early cardiomyopathy can be predicted.

This study will explore biomarker discovery by analysing an age/gender matched subgroup for the top differentially expressed microRNA and protein biomarkers. Selected biomarkers will then be validated in a larger cohort.

Condition or Disease	Intervention/Treatment	Phase
Anthracycline Induced Cardiotoxicity

Detailed Description

CLINICAL APPOINTMENT A linked anonymised Case Report Form will be completed using participant answers and relevant aspects of their electronic care record. This will involve questions about the patient's demographics, chemotherapy history, cardiac symptoms, past medical history, medication history and family history.

Consenting patients will then have

height, weight and blood pressure taken
cardiovascular and respiratory examination Participants will then undergo
SF36 quality of life questionnaire
6 minute walk test
Electrocardiogram by a trained researcher
Venesection- 40ml blood sample from a peripheral vein by the trained researcher

INVESTIGATIONS

Participants will be invited for:

24 hour holter monitor- arrhythmia assessment
Echocardiogram- diastolic and systolic function assessment, valvular analysis, global longitudinal strain
Magnetic resonance imaging (MRI) scan of the heart- volumetric analysis, late gadolinium enhancement and STIR imaging assessments. As part of the scan the patient will require a venflon to be inserted into a peripheral vein for gadolinium injection. A safety questionnaire will be sent to the patient prior to attendance as part of standard MRI procedure. All safety aspects will be re-assessed on the day of attendance by a trained radiographer

BLOOD SAMPLE ANALYSIS Blood samples will be sent for standard of care and cardiovascular risk assessment. Tests include a full blood picture, urea and electrolytes, C-reactive protein, iron profile, B12 and folate, lipid profile, HbA1c, NT-proBNP and high sensitivity troponin.

Additional disease associated biomarkers for example sST2, MPO, and IL6 will be quantified using immunoassays. Biomarker discovery, including transcriptomics and proteomics will be carried out to identify signatures that could predict cardiotoxicity, subclinical dysfunction, and cardiomyopathy.

Study Design

Study Type:

Observational

Anticipated Enrollment :

208 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Early Detection of Late Anthracycline Induced Cardiotoxicity in Survivors of Childhood Malignancy

Anticipated Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Outcome Measures

Primary Outcome Measures

Cardiotoxicity [2 years]
Number of participants with anthracycline related cardiotoxicity as defined by the British Society of Echocardiography and British Cardio-Oncology Society guidelines

Secondary Outcome Measures

Incidence of myocardial injury [2 years]
Levels of high sensitivity troponin T and NT-proBNP

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

-Male and female patients over the age of 18 who have received at least moderate (100mg/m2) anthracycline chemotherapy as a child (<16 years).

Exclusion Criteria:

patients born with complex heart disease
patients who would not be safely able to have a magnetic resonance imaging scan
patients who cannot give consent
patients under the age of 18 or who have had less than a moderate dose of anthracycline