Cardiotoxicity in doxorubicin-treated patients Circulatory System
Conditions
Interventions
Participants will be recruited to the study by the clinical team by means of a verbal explanation and the provision of a Patient Information Sheet (PIS). Potential participants may provide their conta
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cardiotoxicity cohort: 1. Over 16 years of age at the time of consent 2. Capable of providing informed consent as determined by the consenting clinician 3. Receiving doxorubicin chemotherapy treatment at the time of consent or previously received doxorubicin chemotherapy treatment prior to consent 4. Clinical presentation of left ventricular systolic dysfunction at the time of consent secondary to receiving doxorubicin chemotherapy treatment as determined by the clinical team Non-cardiotoxicity cohort: 1. Over 16 years of age at the time of consent 2. Capable of providing informed consent as determined by the consenting clinician 3. Receiving doxorubicin chemotherapy treatment at the time of consent or previously received doxorubicin chemotherapy treatment prior to consent 4. Normal left ventricular systolic function at the time of consent secondary to receiving doxorubicin chemotherapy treatment as determined by the clinical team
Exclusion criteria
Exclusion criteria: 1. Under 16 years of age at the time of consent 2. Lacking ability to provide informed consent as determined by the consenting clinician 3. Judged to have been coerced to consent as determined by the consenting clinician 4. Pre-existing left ventricular systolic dysfunction to be reviewed by the clinical team on a case by case basis 5. Recent surgery (30 units a week) and/or recreational drug use 7. Active immunological disease as determined by the clinical team 8. On current steroid therapy with the exception of corticosteroid inhaler <2 mg/kg 9. Active or recent (<6 weeks) serious infection at the discretion of the clinical team 10. Inability to comply with study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Reprogramming efficiency of PBMC into iPSC determined by PCR and ICC after colony formation 2. Chromosomal stability determined by karyotype analysis at 2-6 weeks after colony formation 3. Differentiation efficiency of iPSC into cardiomyocytes determined by ICC at 10-14 days after initiation 4. Amenability of iPSC and cardiomyocytes to experimental analysis determined by PCR, ICC, electrophysiology, and Western blotting at 1-2 weeks after formation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. A doxorubicin-specific signature in cardiomyocytes derived from cardiotoxicity subjects, identified using proteomics profiling at 3 weeks 2. Candidate biomarkers that are of functional relevance to doxorubicin-induced cardiotoxicity, identified by proteomics profiling at 3 weeks | — |
Countries
England, United Kingdom
Outcome results
None listed