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Effect of Anthracyclines and Cyclophosphamide on Cardiovascular Responses

Primary Purpose

Cardiotoxicity, Cardiovascular Disease, Neurovascular Disorder

Status
Recruiting
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Physical Characteristics
Muscular Sympathetic Nervous Activity
Cardiac Function
Heart rate
Blood pressure
Blood Assessments
Muscle blood flow
Endothelium-dependent vascular function
Vascular intima-media thickness
Physical Capacity
Anthracycline & Cyclophosphamide treatment scheme
Sponsored by
University of Sao Paulo General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Cardiotoxicity focused on measuring Chemotherapy, Endothelial Disfunction, Muscle Sympathetic Nerve Activity, Blood Pressure

Eligibility Criteria

45 Years - 60 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

pre and post chemotherapy assessments

Arm Description

The patients will be assessed before and after chemotherapy treatment.

Outcomes

Primary Outcome Measures

Muscle sympathetic nerve activity
Change in muscular sympathetic nerve activity measured by microneurography

Secondary Outcome Measures

Muscle blood flow
Change in muscle blood flow measured by venous oclusion plethysmography
Blood Pressure
Change in blood pressure measured by finometer
Physical capacity
Change in physical capacity measured by cardiopulmonary exercise test
Cardiac Function Impairment
Change in cardiac function measured by echocardiography

Full Information

First Posted
August 26, 2020
Last Updated
June 12, 2023
Sponsor
University of Sao Paulo General Hospital
Collaborators
Universidade Federal Fluminense, Hospital Israelita Albert Einstein
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1. Study Identification

Unique Protocol Identification Number
NCT04568161
Brief Title
Effect of Anthracyclines and Cyclophosphamide on Cardiovascular Responses
Official Title
Chronic Effect of Doxorubicin and Cyclophosphamide on Neurovascular Control and Blood Pressure in Women in Adjuvant Treatment for Breast Neoplasia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 3, 2020 (Actual)
Primary Completion Date
September 3, 2022 (Actual)
Study Completion Date
November 3, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Sao Paulo General Hospital
Collaborators
Universidade Federal Fluminense, Hospital Israelita Albert Einstein

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiotoxicity, Cardiovascular Disease, Neurovascular Disorder, Endothelial Disfunction, Breast Cancer
Keywords
Chemotherapy, Endothelial Disfunction, Muscle Sympathetic Nerve Activity, Blood Pressure

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
pre and post chemotherapy assessments
Arm Type
Experimental
Arm Description
The patients will be assessed before and after chemotherapy treatment.
Intervention Type
Procedure
Intervention Name(s)
Physical Characteristics
Intervention Description
Body weight, height and waist circumference
Intervention Type
Procedure
Intervention Name(s)
Muscular Sympathetic Nervous Activity
Intervention Description
Microneurography technique.
Intervention Type
Diagnostic Test
Intervention Name(s)
Cardiac Function
Intervention Description
Echocardiography.
Intervention Type
Diagnostic Test
Intervention Name(s)
Heart rate
Intervention Description
Electrocardiography
Intervention Type
Diagnostic Test
Intervention Name(s)
Blood pressure
Intervention Description
Non-invasive photoplethysmography.
Intervention Type
Diagnostic Test
Intervention Name(s)
Blood Assessments
Intervention Description
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
Intervention Name(s)
Muscle blood flow
Intervention Description
Venous occlusion plethysmography
Intervention Type
Diagnostic Test
Intervention Name(s)
Endothelium-dependent vascular function
Intervention Description
Brachial ultrasound
Intervention Type
Diagnostic Test
Intervention Name(s)
Vascular intima-media thickness
Intervention Description
Carotid ultrasound
Intervention Type
Diagnostic Test
Intervention Name(s)
Physical Capacity
Intervention Description
Cardiopulmonary exercise test
Intervention Type
Drug
Intervention Name(s)
Anthracycline & Cyclophosphamide treatment scheme
Intervention Description
Four session of intravenous (in bolus) infusion of doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 with an interval of 21 days between sessions.
Primary Outcome Measure Information:
Title
Muscle sympathetic nerve activity
Description
Change in muscular sympathetic nerve activity measured by microneurography
Time Frame
15-20 days after the end of AC regimen
Secondary Outcome Measure Information:
Title
Muscle blood flow
Description
Change in muscle blood flow measured by venous oclusion plethysmography
Time Frame
15-20 days after the end of AC regimen
Title
Blood Pressure
Description
Change in blood pressure measured by finometer
Time Frame
15-20 days after the and of AC regimen
Title
Physical capacity
Description
Change in physical capacity measured by cardiopulmonary exercise test
Time Frame
15-20 days after the end of AC regimen
Title
Cardiac Function Impairment
Description
Change in cardiac function measured by echocardiography
Time Frame
15-20 days after the end of AC regimen

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Raphaela VR Groehs, PhD
Phone
551126615699
Email
rapha_vilar@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ursula Urias, PhD
Phone
551126615699
Email
uurias@usp.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos E Negrao, PhD
Organizational Affiliation
Instituto do Coracao, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo
City
Sao Paulo
ZIP/Postal Code
05403-900
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raphaela VR Groehs, PhD
Phone
551126615699
Email
rapha_vilar@hotmail.com
First Name & Middle Initial & Last Name & Degree
Ursula Urias, PhD
Phone
551126615699
Email
uurias@usp.br
First Name & Middle Initial & Last Name & Degree
Carlos Eduardo Negrao, PHD

12. IPD Sharing Statement

Plan to Share IPD
No
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Effect of Anthracyclines and Cyclophosphamide on Cardiovascular Responses

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