Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping

NCT ID: NCT06048458

Last Updated: 2023-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

75 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-05-18

Study Completion Date

2024-02-29

Brief Summary

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Observational prospective cohort study designed to assess the mechanisms of fluoropyrimidine induced cardiovascular toxicity.

Detailed Description

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Fluoropyrimidine (5-FU and Capecitabine) based chemotherapy regimens form the cornerstone of treatments for gastrointestinal (GI) cancers. Fluoropyrimidines however, are associated with the development of cardiovascular toxicity which can take on different forms including chest pain, myocardial infarction, arrhythmias, heart failure and sudden death. The underlying mechanisms of cardiovascular toxicity are not fully understood.

The investigators will use quantitative cardiovascular magnetic resonance perfusion imaging, CT coronary angiography, extra-cardiac vascular assessments and serum cardiac biomarkers to improve insights into the pathophysiology of fluoropyrimidine cardiotoxicity. All enrolled participants in this two centre study will have GI cancers requiring treatment with fluoropyrimidine chemotherapy.

Conditions

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Cardiovascular Diseases Cardiotoxicity Fluorouracil Adverse Reaction Malignancy Colorectal Cancer Oesophagus Cancer Gastric Cancer Pancreatic Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort 1

Stable patients with gastrointestinal malignancies will be recruited to this 3 timepoint study prior to initiation of fluoropyrimidine chemotherapy. All investigations will be performed at baseline, at the end of cycle 1 and 4-6 weeks post completion of treatment.

Cardiovascular magnetic resonance with stress perfusion

Intervention Type DIAGNOSTIC_TEST

Cardiac MRI scan to assess changes in left ventricular function, parametric mapping, strain and myocardial blood flow. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

CT coronary angiography

Intervention Type DIAGNOSTIC_TEST

CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease

Retinal OCT angiography

Intervention Type DIAGNOSTIC_TEST

Retinal OCTa to assess changes in retinal vasculature. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Sublingual microscopy (GlycoCheck)

Intervention Type DIAGNOSTIC_TEST

To determine changes in sublingual microvascular health. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)

Intervention Type DIAGNOSTIC_TEST

Performed to assess for myocardial injury. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Cohort 2

Patients with gastrointestinal malignancies presenting to hospital with acute symptoms of fluoropyrimidine cardiotoxicity. All investigations will be performed during the acute presentation and the second visit will be performed 4-6 weeks post completion of treatment.

Cardiovascular magnetic resonance with stress perfusion

Intervention Type DIAGNOSTIC_TEST

Cardiac MRI scan to assess changes in left ventricular function, parametric mapping, strain and myocardial blood flow. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

CT coronary angiography

Intervention Type DIAGNOSTIC_TEST

CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease

Retinal OCT angiography

Intervention Type DIAGNOSTIC_TEST

Retinal OCTa to assess changes in retinal vasculature. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Sublingual microscopy (GlycoCheck)

Intervention Type DIAGNOSTIC_TEST

To determine changes in sublingual microvascular health. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)

Intervention Type DIAGNOSTIC_TEST

Performed to assess for myocardial injury. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Interventions

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Cardiovascular magnetic resonance with stress perfusion

Cardiac MRI scan to assess changes in left ventricular function, parametric mapping, strain and myocardial blood flow. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Intervention Type DIAGNOSTIC_TEST

CT coronary angiography

CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease

Intervention Type DIAGNOSTIC_TEST

Retinal OCT angiography

Retinal OCTa to assess changes in retinal vasculature. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Intervention Type DIAGNOSTIC_TEST

Sublingual microscopy (GlycoCheck)

To determine changes in sublingual microvascular health. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Intervention Type DIAGNOSTIC_TEST

Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)

Performed to assess for myocardial injury. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Age \>18 years
* Gastrointestinal malignancy
* Receiving fluoropyrimidine chemotherapy

Exclusion Criteria

* Participants unable or unwilling to provide consent
* Participants that have a conventional contraindication for magnetic resonance imaging (MRI) including permanent implantable cardiac devices, ferromagnetic implants, pregnancy, large body size not fitting into the scanner bore and severe claustrophobia will be excluded
* Participants that have a conventional contraindication for adenosine stress perfusion including a history of trifascicular block or of second-degree heart block or higher on ECG, or uncontrolled asthma.
* Participants with significant renal impairment (eGFR\<30ml/min)
* History of allergy to adenosine, gadolinium or iodinated contrast
* Patients with terminal illness (life expectancy \<6 months) will be excluded.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Charlotte Manisty, PhD

Role: PRINCIPAL_INVESTIGATOR

UCL

Locations

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St Bartholomews Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Aderonke Abiodun, MBChB

Role: CONTACT

02073777000

Facility Contacts

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Aderonke Abiodun, MBChB

Role: primary

Other Identifiers

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142669

Identifier Type: -

Identifier Source: org_study_id

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