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Cardiovascular Complications of Carfilzomib Treatment

NCT03543579 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 46

Last updated 2021-04-28

No results posted yet for this study

Summary

Accumulating evidence supports the hypothesis of a pathophysiological role of the Ubiquitin Proteasome System (UPS) in the process of atherosclerosis and vascular function. However the data are contradicting in respect to the direction of this association and therefore the net effect of UPS activity on the cardiovascular system is not known. Inhibitors of UPS are currently standard of care for patients with multiple myeloma (MM). Heart failure and hypertension have been reported in studies of carfilzomib, an irreversible 2nd generation proteasome inhibitor, both as a single agent and in combination with other drugs but their potential vascular toxicity is not adequately studied. Furthermore, as the role of the UPS has not been studied yet clinically but only in experimental and autopsy based studies, assessment of UPS inhibition in humans would facilitate understanding of the UPS-mediated pathophysiologic mechanisms in human atherosclerosis. Thus, this project may stimulate further research on the role of UPS in atherogenesis and potential new therapeutic approaches on vascular dysfunction may arise. We designed the following project in order to investigate the acute and chronic effect of Carfilzomib (CFZ) on cardiovascular function. Patients with an indication to receive CFZ will be recruited to be followed in the Clinical Therapeutics Department in pre-specified timepoints. Functional and structural measurements including markers of arterial stiffness and subclinical atherosclerosis will be performed using non-invasive well-validated techniques. Blood pressure will be also evaluated using 24h hour ambulatory monitoring. Evaluation of cardiac function will be performed at baseline and thereafter at 6 months or earlier if a suspicious event occurs necessitating evaluation of cardiac function. In parallel and at each time point, the activity of UPS and intracellular levels of ubiquitin conjugates will be measured in peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs) using enzymatic proteasome activity assays and western blot techniques, respectively.

Conditions

Sponsors & Collaborators

  • University of Athens

    lead OTHER

Principal Investigators

  • Efstathios Kastritis, Professor · Associate Professor of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece

  • Kimon Stamatelopoulos, Professor · Assistant Professor of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece

Eligibility

Min Age
18 Years
Max Age
90 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-03-23
Primary Completion
2019-10-30
Completion
2021-12-31

Countries

  • Greece

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03543579 on ClinicalTrials.gov