Late Anthracycline Induced Cardiotoxicity- Childhood Cancer Survivors

February 19, 2024 updated by: Chris Watson, Queen's University, Belfast

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

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.

Study Overview

Status

Active, not recruiting

Conditions

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, grip strength
  • Electrocardiogram by a trained researcher
  • Venesection- 40ml blood sample from a peripheral vein by the trained researcher Crevicular fluid sample

INVESTIGATIONS

Participants will be invited for:

  1. 24 hour holter monitor- arrhythmia assessment
  2. Echocardiogram- diastolic and systolic function assessment, valvular analysis, global longitudinal strain
  3. 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 Type

Observational

Enrollment (Actual)

103

Contacts and Locations

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

Study Locations

  • United Kingdom
      • Belfast, United Kingdom, BT9 7AB
        • Belfast Health and Social Care Trust

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients identified by paediatric oncology who have received anthracycline therapy in childhood.

Description

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiotoxicity
Time Frame: 2 years
Number of participants with anthracycline related cardiotoxicity as defined by the British Society of Echocardiography and British Cardio-Oncology Society guidelines
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of myocardial injury
Time Frame: 2 years
Levels of high sensitivity troponin T and NT-proBNP
2 years

Collaborators and Investigators

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

Sponsor

Queen's University, Belfast

Investigators

  • Principal Investigator: Lana J Dixon, MB BCh BAO, National Health Service, United Kingdom

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)

October 20, 2021

Primary Completion (Estimated)

April 1, 2024

Study Completion (Estimated)

April 1, 2024

Study Registration Dates

First Submitted

April 1, 2021

First Submitted That Met QC Criteria

April 19, 2021

First Posted (Actual)

April 21, 2021

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 19, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B21/01

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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