Effect of Anthracyclines and Cyclophosphamide on Cardiovascular Responses

NCT ID: NCT04568161

Last Updated: 2025-04-03

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

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-03

Study Completion Date

2025-03-03

Brief Summary

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The present study aims to investigate the chronic effect of treatment with doxorubicin and cyclophosphamide on neurovascular control and blood pressure in women undergoing adjuvant treatment for breast cancer.

Detailed Description

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The development of new drugs and different adjuvant therapeutic regimens, based on the combination of anthracycline (A) and cyclophosphamide (C), have contributed greatly to improve survival rate in breast cancer patients. Despite the clinical benefits of this therapy, AC treatment can cause cardiovascular acute and chronic changes. In a recent investigation, we observed that an acute AC chemotherapy session increases sympathetic nervous activity and blood pressure in patients with breast cancer.

The present study aims to investigate the chronic effects of AC regimen on sympathetic nervous activity, peripheral vasoconstriction, endothelial microparticles and blood pressure, in women with breast cancer.

Conditions

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Cardiotoxicity Cardiovascular Disease Neurovascular Disorder Endothelial Disfunction Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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pre and post chemotherapy assessments

The patients will be assessed before and after chemotherapy treatment.

Group Type EXPERIMENTAL

Physical Characteristics

Intervention Type PROCEDURE

Body weight, height and waist circumference

Muscular Sympathetic Nervous Activity

Intervention Type PROCEDURE

Microneurography technique.

Cardiac Function

Intervention Type DIAGNOSTIC_TEST

Echocardiography.

Heart rate

Intervention Type DIAGNOSTIC_TEST

Electrocardiography

Blood pressure

Intervention Type DIAGNOSTIC_TEST

Non-invasive photoplethysmography.

Blood Assessments

Intervention Type DIAGNOSTIC_TEST

Serum and Plasma will be extracted by centrifugation. Endothelial microparticles by flow cytometry Interleukin-6 and tumor necrosis factor α by ELISA, High-sensitive reactive serum C-reactive protein by immunoturbidimetric assay, NT- ProBNP According to Central Laboratory, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Endothelin-1 by immunoenzymatic method Nitric oxide by gas chemiluminescence Lipoperoxidation by fluorimetry Carbonyl by spectrophotometer, and Superoxide Dismutase (SOD) by colorimetry.

Muscle blood flow

Intervention Type DIAGNOSTIC_TEST

Venous occlusion plethysmography

Endothelium-dependent vascular function

Intervention Type DIAGNOSTIC_TEST

Brachial ultrasound

Vascular intima-media thickness

Intervention Type DIAGNOSTIC_TEST

Carotid ultrasound

Physical Capacity

Intervention Type DIAGNOSTIC_TEST

Cardiopulmonary exercise test

Anthracycline & Cyclophosphamide treatment scheme

Intervention Type DRUG

Four session of intravenous (in bolus) infusion of doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 with an interval of 21 days between sessions.

Interventions

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Physical Characteristics

Body weight, height and waist circumference

Intervention Type PROCEDURE

Muscular Sympathetic Nervous Activity

Microneurography technique.

Intervention Type PROCEDURE

Cardiac Function

Echocardiography.

Intervention Type DIAGNOSTIC_TEST

Heart rate

Electrocardiography

Intervention Type DIAGNOSTIC_TEST

Blood pressure

Non-invasive photoplethysmography.

Intervention Type DIAGNOSTIC_TEST

Blood Assessments

Serum and Plasma will be extracted by centrifugation. Endothelial microparticles by flow cytometry Interleukin-6 and tumor necrosis factor α by ELISA, High-sensitive reactive serum C-reactive protein by immunoturbidimetric assay, NT- ProBNP According to Central Laboratory, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Endothelin-1 by immunoenzymatic method Nitric oxide by gas chemiluminescence Lipoperoxidation by fluorimetry Carbonyl by spectrophotometer, and Superoxide Dismutase (SOD) by colorimetry.

Intervention Type DIAGNOSTIC_TEST

Muscle blood flow

Venous occlusion plethysmography

Intervention Type DIAGNOSTIC_TEST

Endothelium-dependent vascular function

Brachial ultrasound

Intervention Type DIAGNOSTIC_TEST

Vascular intima-media thickness

Carotid ultrasound

Intervention Type DIAGNOSTIC_TEST

Physical Capacity

Cardiopulmonary exercise test

Intervention Type DIAGNOSTIC_TEST

Anthracycline & Cyclophosphamide treatment scheme

Four session of intravenous (in bolus) infusion of doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 with an interval of 21 days between sessions.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* diagnosis of stage II-III breast cancer
* starting adjuvant chemotherapy

Exclusion Criteria

* metastatic disease,
* hypercholesterolemia, diabetes,
* hypertension,
* severe lymphedema,
* organic disorders (renal failure, heart failure and chronic liver disease),
* obesity (BMI\> 30) and,
* who are under pharmacological treatment with statins, angiotensin-converting enzyme inhibitors, losartan potassium, beta blockers or antioxidants
Minimum Eligible Age

45 Years

Maximum Eligible Age

60 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Universidade Federal Fluminense

OTHER

Sponsor Role collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role collaborator

University of Sao Paulo General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carlos E Negrao, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto do Coracao, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo

Locations

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Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo

São Paulo, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Jensen BV, Skovsgaard T, Nielsen SL. Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol. 2002 May;13(5):699-709. doi: 10.1093/annonc/mdf132.

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Laterza MC, de Matos LD, Trombetta IC, Braga AM, Roveda F, Alves MJ, Krieger EM, Negrao CE, Rondon MU. Exercise training restores baroreflex sensitivity in never-treated hypertensive patients. Hypertension. 2007 Jun;49(6):1298-306. doi: 10.1161/HYPERTENSIONAHA.106.085548. Epub 2007 Apr 16.

Reference Type BACKGROUND
PMID: 17438307 (View on PubMed)

Barretto AC, Santos AC, Munhoz R, Rondon MU, Franco FG, Trombetta IC, Roveda F, de Matos LN, Braga AM, Middlekauff HR, Negrao CE. Increased muscle sympathetic nerve activity predicts mortality in heart failure patients. Int J Cardiol. 2009 Jul 10;135(3):302-7. doi: 10.1016/j.ijcard.2008.03.056. Epub 2008 Jun 26.

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Reference Type BACKGROUND
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Other Identifiers

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Breast Cancer Chemotherapy

Identifier Type: -

Identifier Source: org_study_id

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