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This study looks to find a causative or predictive aspect of the suPAR biomarker for heart failure in breast cancer patients receiving Doxorubicin drug chemo regimen.
suPAR is a circulating protein which can be found in blood and/or urine and is associated with both kidney and heart disease.
The study will look at suPAR's association with three other biomarkers called troponin, B-Type Natriuretic Peptide (BNP) and C- Reactive Protein (CRP) that are also associated with heart disease.
In this study, the patient will have blood drawn as a routine part of the cancer treatment. That is prior to starting the cancer therapy, then after the first 2 and last 2 doxorubicin cycles (4 cycles altogether); as well as at 3, 6, & 12 months after doxorubicin treatment. (6 Visits in total) The patient will also have an echocardiogram (echo, heart ultrasound) at each of these time points. The first of the six study echos is considered part of the routine care.
Full description
Hypothesis 1: Higher suPAR at baseline will predispose to DOX-induced cardiomyopathy to be observed by histology in mouse models, and tested using LVEF (Left Ventricular Ejection Fraction) assessment, and surrogate cardiovascular outcome measures as described in humans.
Hypothesis 2: suPAR is a marker of DOX-induced cardiomyopathy after exposure to DOX, to be observed by histology in mouse models, and tested using surrogate cardiovascular outcome measures as described in humans.
In the laboratory approach of the study, the investigators aimed to establish the role of suPAR in DOX induced cardiomyopathy. The risk for DOX induced cardiomyopathy is known to increase with an increase of the accumulative dose. The investigators therefore used two doses of DOX. One group of mice received weekly injections of DOX at 3mg/kg bodyweight for 6 week (accumulative dose of 18mg/kg: DOX18) whereas another group received an accumulative dose of 25mg/kg bodyweight (DOX25: 5 weeks, at 5 mg/kg bodyweight). Blood samples were taken before the first injection, in the middle of treatment and at the end of treatment or at the day of sacrifice. The bodyweight of the animals was constantly monitored throughout the study.
At time of sacrifice, the heart weight and tibia length of the mice were quantified and cells were isolated to determine cellular levels of reactive oxygen species (ROS), contractility and Ca handling properties.
DOX induced cardiomyopathy can manifest years after treatment. Tissue samples from hearts of the DOX18 and DOX25 treatment group were obtained and quantitative PCR (Polymerase Chain Reaction amplification) of the ventricular tissue will help us determine the changes in protein expression and cellular signaling that underlie these DOX induced changes in cellular function.
Blood samples obtained from the DOX18 and DOX25 mice will be analyzed for their level of suPAR to determine changes in suPAR over the duration of treatment and potential correlations of [suPAR] with the degree of cardiac dysfunction.
The data collected will be analyzed using a descriptive analysis with means and standard deviations for continuous variables and percentages for categorical variables. A paired t-test comparing the pre-post difference will be used to compare the differences in the groups comparing pre to post measures of myocardial damage based on histology for mouse models, and LVEF (Left Ventricular Ejection Fraction) for human data. Analysis will be performed using SAS (statistical analysis software).
The expected results from the data collected in this study aim to both gain an understanding of and describe the relationship of various covariates to primary outcomes.
It is expected to have 50 participants by the study end date. There is a trained team working on the study, insuring quality of data gathering, recruitment and enrollment of patients.
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Data sourced from clinicaltrials.gov
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