Effect of Physical Training in Patients With Heart Failure Caused by Chemotherapy for Cancer Treatment

New therapies for cancer increased patient survival, but led to the recognition of adverse effects associated with cancer treatment, such as the use of chemotherapy. Cardiotoxicity is the most significant adverse effect, which affect the functional capacity and quality of life and is associated with high morbidity and mortality, regardless of the oncological prognosis. One of the manifestations of cardiotoxicity is ventricular dysfunction that can lead to heart failure. Neuro humoral hyperactivation with increased sympathetic nerve activity is a typical manifestation of heart failure and is associated with worse prognosis. Studies have shown that physical training significantly reduces sympathetic nerve activity in addition to improving muscle blood flow, reversing effects on skeletal muscle and improving quality of life. The hypothesis is that physical training may reduce sympathetic nerve activity and vasoconstrictor status in patients with heart failure caused by anthracyclines, as well as improving baroreflex and chemoreflex sensibility, mechanoreflex and metaborreflex control and skeletal myopathy.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Cancer; Cardiotoxicity; Insufficiency;Cardiac
• Intervention / Treatment: Other: exercise training

Detailed Description

The investigators included patients> 18 years, left ventricular ejection fraction <= 0.55, functional class (NYHA) I-III, under medical treatment for heart failure. Patients with coronary artery disease, moderate to severe valve disease, positive Chagas serology, inability to participate in an exercise program are excluded.

Primary outcome: Muscle sympathetic nerve activity Secondary outcome: arterial baroreflex sensitivity, peripheral chemorreflex sensitivity, mecanic and muscuclar metaborreflex control, ubiquitin proteasome system activity.

Patients were divided into 2 groups-trained (n = 10) and non-trained (n = 10). Patients in the trained group will complete 16 weeks of aerobic training. Evaluation of cardiac function, functional capacity, quality of life and biochemical evaluation (troponin, hs-CRP and BNP). For muscle evaluation will be performed biopsy of the vastus lateralis muscle

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amanda Gonzales Rodrigues; Phone Number: +55(11)999468264; Email: amanda.rodrigues@incor.usp.br
• Study Contact Backup: Name: Carlos Eduardo Negrao, PHD; Phone Number: +55(11)26615043

Study Locations

• Brazil
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-900
      • Recruiting
      • Heart Institute of University of São Paulo
      • Contact: Amanda Gonzales Rodrigues; Phone Number: +55(11)999468264; Email: amanda.rodrigues@incor.usp.br
      • Contact: Carlos Eduardo Negrao, PHD; Phone Number: +55(11)26615043; Email: carlos.negrao@incor.usp.br
      • Principal Investigator: Roberto Kalil Filho, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18 years old
• Funcional Class I-III (NYHA)
• Ejection fraction < o,55
• treated for heart failure

Exclusion Criteria:

• Coronary artery disease
• Moderate to major valve disease
• Positive serology for Chagas
• Inability to perform physical exercises

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group; A group of patients who will not be trained will be evaluated at baseline (pre) and after 16 weeks. They are oriented to maintain lifestyle changes
Experimental: Training group; Patients will complete 16 weeks of training including 40 minutes of aerobic training, 15 minutes of resistive exercise and 5 minutes of relaxation.	Other: exercise training; Patients undergo 16 weeks of physical training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure muscular sympathetic nervous activity	The sympathetic nervous activity is assessed by the microneurography technique	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate baroreflex activity	Evaluation of muscular sympathetic nervous activity at rest by the technique of microneurography, evaluation of the muscular blood flow by venous occlusion plethysmography technique	16 weeks
Evaluate quimiorreflex sensibility	Evaluation of muscular sympathetic nervous activity at rest by the technique of microneurography, evaluation of the muscular blood flow by venous occlusion plethysmography technique	16 weeks
Evaluate Mecanorreflex control	Evaluation of muscular sympathetic nervous activity at rest by the technique of microneurography, evaluation of the muscular blood flow by venous occlusion plethysmography technique	16 weeks
Evaluate metaborreflex control	Evaluation of muscular sympathetic nervous activity at rest by the technique of microneurography, evaluation of the muscular blood flow by venous occlusion plethysmography technique	16 weeks
Evaluation of skeletal myopathy	muscle biopsy	16 weeks

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: InCor Heart Institute; Hospital Sirio-Libanes; Cancer Institute of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2016
• Primary Completion (Anticipated): February 1, 2021
• Study Completion (Anticipated): February 1, 2021

Study Registration Dates

• First Submitted: March 29, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): August 7, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: autonomic dysfunction; baroreflex control; ergorreflex control; muscle myopaty
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Heart Failure; Cardiotoxicity
• Other Study ID Numbers: SDC COP 002/15/002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No