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Neurovascular Changes Induced by Chemotherapy

Primary Purpose

Breast Cancer, Chemotherapeutic Toxicity

Status
Completed
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Chemotherapy
Sponsored by
University of Sao Paulo General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Breast Cancer focused on measuring Chemotherapy, Muscle sympathetic nervous activity, Blood flow, Endothelial microparticles

Eligibility Criteria

35 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Breast cancer patients and prescription of adjuvant chemotherapy with antracycline and cyclophosphamide

Exclusion Criteria:

  • Metastic disease
  • Hypercholesterolemia
  • Diabetes
  • Hypertension
  • Severe lymphedema
  • Renal insufficient
  • Heart failure
  • Chronic liver disease
  • Obesity, and treatment with some medications that inhibit cardiotoxicity, as beta-blocker angiotensin converting enzyme, statin, losartan and antioxidants.

Sites / Locations

  • Heart Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemotherapy

Arm Description

Infusion of doxorubicin and cyclophosphamide

Outcomes

Primary Outcome Measures

Neural change induced by chemoterapy
Increase of muscle nerve sympathetic activivity

Secondary Outcome Measures

Vascular change induced by chemoterapy
Decrease of blood flow

Full Information

First Posted
October 25, 2017
Last Updated
November 7, 2017
Sponsor
University of Sao Paulo General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03339804
Brief Title
Neurovascular Changes Induced by Chemotherapy
Official Title
Neurovascular Changes Provoked by Acute Administration Doxorubicin and Cyclophosphamide in Patients With Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
February 22, 2016 (Actual)
Primary Completion Date
December 1, 2016 (Actual)
Study Completion Date
October 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Sao Paulo General Hospital

4. Oversight

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

5. Study Description

Brief Summary
The purpose of the present study was to test the hypothesis that doxorubicin and cyclophosphamide adjuvant chemotherapy (CHT) acutely induces neurovascular and hemodynamic changes in patients with breast cancer. To test this hypothesis, women with breast cancer (stage II-III) underwent two experimental sessions, saline (SL) and CHT. In the CHT session, doxorubicin (60 mg/m2) and cyclophosphamide (600mg/m2) were administred in 45 min. In the SL session, a matching saline volume to that of the CHT session was infused over 45 min.
Detailed Description
The purpose of the present study was to test the hypothesis that doxorubicin and cyclophosphamide adjuvant chemotherapy (CHT) acutely induces neurovascular and hemodynamic changes in patients with breast cancer. To test this hypothesis, the patients were submitted in two experimental sessions, saline and chemotherapy, respectively. Saline Session. After fasting for 2 hours and abstaining from caffeine for 24 hours, the patients were positioned in a supine position. An intra-venous catheter was placed into the brachial venous in the contralateral arm of the breast surgery. Microelectrodes were positioned for MSNA measures in right leg, cuffs were placed around the leg for blood flow assessments and finger cuff was placed in 3 finger of hand for measurement of hemodynamic variables. After the instrumentation, an interval of 10 minutes was allowed, followed by blood sample collections for measurement of MPEs and, hemodynamic and neurovascular measures by period of 15 minutes (pre-infusion). Then, dexamethasone 20 mg and ondansetron 8 mg were administered i.v., followed by saline 0,09%, during 45 minutes. During saline infusion were continuously measured the neurovascular and hemodynamic variables. Finally, after saline administration, another blood sample was collected for MPEs dosing, followed by continuous measurement of hemodynamic and neurovacular variables by 15 minutes period (Figure 1). Chemotherapy session. After a 2 to 3 day-interval, the patients were again positioned in a supine position in a temperature-controlled room (22oC). An intra-venous catheter was placed into the brachial venous in the contralateral arm of the breast surgery. Then, microelectrodes were positioned in the contralateral leg of the first session for MSNA measures. Likewise, cuffs were placed around the contralateral leg of the first protocol for blood flow assessments. After the instrumentation, an interval of 10 minutes was allowed, followed by blood sample collections and basal hemodynamic and neurovascular measures. Then, dexamethasone 20 mg and ondansetron 8 mg were administered, i.v., followed by doxorubicin and cyclophosphamide, during 45 minutes. During doxorubicin and cyclophosphamide infusions were continuously measured the neurovascular and hemodynamic variables. Finally, after doxorubicin plus cyclophosphamide administration, another blood sample was collected for EMPs dosing, followed by continuous measurement of hemodynamic and neurovacular variables by 15 minutes period

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Chemotherapeutic Toxicity
Keywords
Chemotherapy, Muscle sympathetic nervous activity, Blood flow, Endothelial microparticles

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy
Arm Type
Experimental
Arm Description
Infusion of doxorubicin and cyclophosphamide
Intervention Type
Other
Intervention Name(s)
Chemotherapy
Other Intervention Name(s)
Doxorubicin and cyclophosphamide
Intervention Description
In chemoteraphy session, doxorubicin (60 mg/m2) and cyclophosphamide (600mg/m2) were administred in 45 min
Primary Outcome Measure Information:
Title
Neural change induced by chemoterapy
Description
Increase of muscle nerve sympathetic activivity
Time Frame
10 min
Secondary Outcome Measure Information:
Title
Vascular change induced by chemoterapy
Description
Decrease of blood flow
Time Frame
10 min
Other Pre-specified Outcome Measures:
Title
Hemodynamic change induced by chemoterapy
Description
Increase of blood pressure
Time Frame
10 min

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Breast cancer patients and prescription of adjuvant chemotherapy with antracycline and cyclophosphamide Exclusion Criteria: Metastic disease Hypercholesterolemia Diabetes Hypertension Severe lymphedema Renal insufficient Heart failure Chronic liver disease Obesity, and treatment with some medications that inhibit cardiotoxicity, as beta-blocker angiotensin converting enzyme, statin, losartan and antioxidants.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Negrão
Organizational Affiliation
University of São Paulo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Heart Institute
City
São Paulo
State/Province
Cerqueira Cesar
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No

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Neurovascular Changes Induced by Chemotherapy

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