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CardiotoxicityNCT04568161

Effect of Anthracyclines and Cyclophosphamide on Cardiovascular Responses

A study testing Physical Characteristics, Muscular Sympathetic Nervous Activity and Cardiac Function in people with Cardiotoxicity and Cardiovascular Disease, run by University of Sao Paulo General Hospital at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 45 to 60 years, women only
What is being tested?
Physical Characteristics, Muscular Sympathetic Nervous Activity and Cardiac Function
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteBrazil
Study dates
3 Aug 2020to 3 Mar 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 60 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Brazil1 site

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

    São Paulo, São Paulo, 05403-900

Other trials in Brazil

About this study

Official title: Chronic Effect of Doxorubicin and Cyclophosphamide on Neurovascular Control and Blood Pressure in Women in Adjuvant Treatment for Breast Neoplasia

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.

Read the 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.

Being tested
Physical Characteristics, Muscular Sympathetic Nervous Activity, Cardiac Function, Heart rate, Blood pressure
Keywords
Chemotherapy, Endothelial Disfunction, Muscle Sympathetic Nerve Activity, Blood Pressure
Medical subject headings
Cardiotoxicity, Cardiovascular Diseases, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Physical CharacteristicsProcedure or surgery

    Body weight, height and waist circumference

  • Muscular Sympathetic Nervous ActivityProcedure or surgery

    Microneurography technique.

  • Cardiac FunctionDiagnostic test

    Echocardiography.

  • Heart rateDiagnostic test

    Electrocardiography

  • Blood pressureDiagnostic test

    Non-invasive photoplethysmography.

  • Blood AssessmentsDiagnostic 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 flowDiagnostic test

    Venous occlusion plethysmography

  • Endothelium-dependent vascular functionDiagnostic test

    Brachial ultrasound

  • Vascular intima-media thicknessDiagnostic test

    Carotid ultrasound

  • Physical CapacityDiagnostic test

    Cardiopulmonary exercise test

  • Anthracycline & Cyclophosphamide treatment schemeDrug

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

Study groups in NCT04568161
Study groupRoleWhat they receive
pre and post chemotherapy assessmentsExperimentalThe patients will be assessed before and after chemotherapy treatment.
Receives: Procedure: Physical Characteristics; Procedure: Muscular Sympathetic Nervous Activity; Diagnostic Test: Cardiac Function; Diagnostic Test: Heart rate; Diagnostic Test: Blood pressure; Diagnostic Test: Blood Assessments; Diagnostic Test: Muscle blood flow; Diagnostic Test: Endothelium-dependent vascular function; Diagnostic Test: Vascular intima-media thickness; Diagnostic Test: Physical Capacity; Drug: Anthracycline & Cyclophosphamide treatment scheme

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Muscle sympathetic nerve activity

    Change in muscular sympathetic nerve activity measured by microneurography

    Measured: 15-20 days after the end of AC regimen

Secondary outcomes (4)

  1. Muscle blood flow

    Change in muscle blood flow measured by venous oclusion plethysmography

    Measured: 15-20 days after the end of AC regimen

  2. Blood Pressure

    Change in blood pressure measured by finometer

    Measured: 15-20 days after the and of AC regimen

  3. Physical capacity

    Change in physical capacity measured by cardiopulmonary exercise test

    Measured: 15-20 days after the end of AC regimen

  4. Cardiac Function Impairment

    Change in cardiac function measured by echocardiography

    Measured: 15-20 days after the end of AC regimen

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2020
  2. Study start3 Aug 2020
  3. Primary completion3 Sep 2022
  4. Study completion3 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04568161
Sponsor's protocol ID
Breast Cancer Chemotherapy
Status last verified
Mar 2025
First submitted
26 Aug 2020
Last updated
3 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019 Jan;69(1):7-34. doi: 10.3322/caac.21551. Epub 2019 Jan 8.

    PubMed 30620402

  • Pai VB, Nahata MC. Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf. 2000 Apr;22(4):263-302. doi: 10.2165/00002018-200022040-00002.

    PubMed 10789823

  • Dolci A, Dominici R, Cardinale D, Sandri MT, Panteghini M. Biochemical markers for prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use. Am J Clin Pathol. 2008 Nov;130(5):688-95. doi: 10.1309/AJCPB66LRIIVMQDR.

    PubMed 18854260

  • 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.

    PubMed 12075737

  • Sales ARK, Negrao MV, Testa L, Ferreira-Santos L, Groehs RVR, Carvalho B, Toschi-Dias E, Rocha NG, Laurindo FRM, Debbas V, Rondon MUPB, Mano MS, Hajjar LA, Hoff PMG, Filho RK, Negrao CE. Chemotherapy acutely impairs neurovascular and hemodynamic responses in women with breast cancer. Am J Physiol Heart Circ Physiol. 2019 Jul 1;317(7):H1-H12. doi: 10.1152/ajpheart.00756.2018. Epub 2019 Apr 19.

    PubMed 31002284

  • Soultati A, Mountzios G, Avgerinou C, Papaxoinis G, Pectasides D, Dimopoulos MA, Papadimitriou C. Endothelial vascular toxicity from chemotherapeutic agents: preclinical evidence and clinical implications. Cancer Treat Rev. 2012 Aug;38(5):473-83. doi: 10.1016/j.ctrv.2011.09.002. Epub 2011 Oct 6.

    PubMed 21982720

  • 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.

    PubMed 17438307

  • 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.

    PubMed 18582965

  • Jenkins NT, Padilla J, Boyle LJ, Credeur DP, Laughlin MH, Fadel PJ. Disturbed blood flow acutely induces activation and apoptosis of the human vascular endothelium. Hypertension. 2013 Mar;61(3):615-21. doi: 10.1161/HYPERTENSIONAHA.111.00561. Epub 2013 Jan 14.

    PubMed 23319545

  • Negrao CE, Rondon MU, Tinucci T, Alves MJ, Roveda F, Braga AM, Reis SF, Nastari L, Barretto AC, Krieger EM, Middlekauff HR. Abnormal neurovascular control during exercise is linked to heart failure severity. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1286-92. doi: 10.1152/ajpheart.2001.280.3.H1286.

    PubMed 11179075

  • Granger DL, Anstey NM, Miller WC, Weinberg JB. Measuring nitric oxide production in human clinical studies. Methods Enzymol. 1999;301:49-61. doi: 10.1016/s0076-6879(99)01068-x. No abstract available.

    PubMed 9919553

  • Kovachich GB, Mishra OP. Lipid peroxidation in rat brain cortical slices as measured by the thiobarbituric acid test. J Neurochem. 1980 Dec;35(6):1449-52. doi: 10.1111/j.1471-4159.1980.tb09022.x.

    PubMed 7441260

  • Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, Zock PL, Taddei S, Deanfield JE, Luscher T, Green DJ, Ghiadoni L. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019 Aug 7;40(30):2534-2547. doi: 10.1093/eurheartj/ehz350.

    PubMed 31211361

  • Abdel-Sayed S, Nussberger J, Aubert JF, Gohlke P, Brunner HR, Brakch N. Measurement of plasma endothelin-1 in experimental hypertension and in healthy subjects. Am J Hypertens. 2003 Jul;16(7):515-21. doi: 10.1016/s0895-7061(03)00903-8.

    PubMed 12850383

Questions about this trial

What is this clinical trial studying?

A study testing Physical Characteristics, Muscular Sympathetic Nervous Activity and Cardiac Function in people with Cardiotoxicity and Cardiovascular Disease, run by University of Sao Paulo General Hospital at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Muscle sympathetic nerve activity (time frame: 15-20 days after the end of AC regimen). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04568161, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2025.

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