We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Exercise Training Following Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02413151
Recruitment Status : Completed
First Posted : April 9, 2015
Results First Posted : April 17, 2019
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
Maria Helena Santa-Clara Pombo Rodrigues, University of Lisbon

Brief Summary:
Cardiac resynchronization therapy(CRT) is recommended to reduce mortality and morbidity in chronic heart failure(CHF) patients New York Heart Association(NYHA) class III-IV who are symptomatic despite optimal medical therapy, with a reduced left ventricular(LV) ejection fraction(LVEF) and prolonged complex QRS. CRT improves the prognosis however, despite the improvement, all major trials have demonstrated that one third of the patients are non-responders to CRT. Three months after the CRT implant, the responders have a significant increase in endothelial function(EntF), a decrease in the LV end-systolic volume, and increase in LVEF, 6 minute walk test(6MWT), improvements in NYHA class and quality of life. It is currently unknown if adding an exercise training(ExT) program following CRT provides better clinical outcomes than CRT alone. Prior studies on CRT and ExT have been preliminary in nature, but suggest small improvements in functional capacity(FC). The correction of endothelial dysfunction is associated with a significant improvement in exercise capacity evidenced by a 26%increase in peak oxygen uptake. These findings are important because CHF patients with the greatest sympathetic activation and the most reduced EntF have the poorest prognosis. Our experience with coronary artery disease patients, and most recently data in patients with CHF show that an ExT program that combines aerobic exercise(AE) and resistance exercise training are more effective than an AE program alone, and the aerobic interval training showed better improvements than continuous endurance training. It is unknown how CHF with more severe functional limitations responds to ExT and, more important, the explanation of the physiological mechanism that can explain the improvements as a consequence of ExT. This lack of scientific information is urgent since this is the group of patients that normally is targeted for CRT. The investigators propose to use a stratified randomized longitudinal study to determine the additional effects of a 6 month ExT in addition to CRT in NYHA stage III-IV HF patients. The aims of the study are:1-to determine whether a long-term ExT program follow the CRT provides better clinical outcomes than CRT alone and 2-To identify the mechanisms of the hypothesize improvement. The results of this project will represent an important contribution by understanding the role of ExT after CRT NYHA stage III-IV heart failure(HF) patients, an understudied population with poor clinical outcome. Understanding the potential mechanisms associated with clinical improvement and outcome is essential for the rehabilitative process to develop new innovative therapies in this high risk population. The investigators will use state-of-art methods including an integrated assessment autonomic nervous system(ANS) and arterial function using 123I-MIBG scintigraphy.

Condition or disease Intervention/treatment Phase
Cardiac Resynchronization Therapy Chronic Heart Failure Behavioral: Exercise training program Device: Cardiac resynchronization therapy (CRT) Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Exercise Training Following Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure
Study Start Date : January 2012
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015


Arm Intervention/treatment
Experimental: Exercise Training Program
The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods.
Behavioral: Exercise training program
The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of peak HR. Each interval, including the last one, is separate by 3 minutes active pauses, walking at 60% to 70% of HRpeak. Total aerobic exercise time at this moment will be 28 minutes and will be maintain to the end of ExT intervention period.

Device: Cardiac resynchronization therapy (CRT)
Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.

Active Comparator: Control
Regular lifestyle
Device: Cardiac resynchronization therapy (CRT)
Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.




Primary Outcome Measures :
  1. Changes in a Composite Measure of Clinical Status - New York Heart Association Functional Class [ Time Frame: 6 months after CRT implantation ]

    The New York Heart Association (NYHA) Functional Classification provides a simple way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina.

    I - Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. no shortness of breath when walking, climbing stairs etc.

    II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.

    III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).

    Comfortable only at rest. IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.


  2. Changes in Cardiac Function - Left Ventricular Ejection Fraction [ Time Frame: 6 months after CRT implantation ]
  3. Changes in Exercise Testing Variables - Maximum Rate of Oxygen Consumption (VO2peak) [ Time Frame: 6 months after CRT implantation ]

Secondary Outcome Measures :
  1. Changes in Exercise Testing Variables - Heart Rate Recovery at 1st Minute (HRR1) [ Time Frame: 6 months after CRT implantation ]
  2. Changes in Inflammatory Markers - Plasmatic Tumor Necrotic Factor Alpha (TNF-alpha) [ Time Frame: 6 months after CRT implantation ]
  3. Changes in Inflammatory Markers - Plasmatic Brain Natriuretic Peptide (BNP) [ Time Frame: 6 months after CRT implantation ]
  4. Changes in a Composite Measure of Quality of Life - HeartQoL T Score [ Time Frame: 6 months after CRT implantation ]
    HeartQoL scale response of 0-3 (poor-better), higher scores indicate better quality of life. Maximum score: 42 (better prognosis); Minimum score:0 (poor prognosis)

  5. Changes in Exercise Testing Variables - Duration of Cardiopulmonary Testing (CPETduration) [ Time Frame: 6 months after CRT implantation ]
  6. Changes in 123I-MIBG Cardiac Scintigraphy - Heart-to-mediastinum Ratio (HMR) Early [ Time Frame: 6 months after CRT implantation ]
  7. Changes in 123I-MIBG Cardiac Scintigraphy - Heart-to-mediastinum Ratio (HMR) Late [ Time Frame: 6 months after CRT implantation ]
  8. Changes in 123I-MIBG Cardiac Scintigraphy - Wash Out (WO) [ Time Frame: 6 months after CRT implantation ]
    washout provides information on the sympathetic drive. The in-vivo visualization of cardiac innervation is evaluated on planar anterior images, which are acquired early and 3 to 5 hours after tracer injection.

  9. Changes in Peripheral Artery Tonometry - Reactive Hyperemia (RHI) [ Time Frame: 6 months after CRT implantation ]
    Reactive hyperaemia index (RHI) is a functional marker of endothelial dysfunction. The RHI was measured using an EndoPAT recorder.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with chronic heart failure (CHF), classified in NYHA functional class III or IV;
  • Receiving optimal medical therapy for CHF (including an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker and a beta-blocker unless a contraindication is evident) with a stable condition for more than 1 month (no hospitalization for HF, no change in medication, and no change in NYHA functional class);
  • Left ventricular ejection fraction (LVEF) < 35%;
  • QRS duration ≥ 120 ms.

Exclusion Criteria:

  • If they are younger than 18 years or are unable to sign informed consent;
  • Patients who had been treated with an intravenous inotropic agent within the 30 days prior to implantation (these medications affect endothelial function after they are discontinued);
  • Unstable angina pectoris;
  • Orthopedic or neurological limitations to exercise.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02413151


Locations
Layout table for location information
Portugal
Santa Marta Hospital
Lisbon, Portugal
Sponsors and Collaborators
University of Lisbon
Investigators
Layout table for investigator information
Principal Investigator: Maria Helena Santa-Clara Pombo Rodrigues, PhD University of Lisbon
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Maria Helena Santa-Clara Pombo Rodrigues, Assistant Professor, University of Lisbon
ClinicalTrials.gov Identifier: NCT02413151    
Other Study ID Numbers: PTDC/DES/120249/2010
First Posted: April 9, 2015    Key Record Dates
Results First Posted: April 17, 2019
Last Update Posted: May 14, 2019
Last Verified: May 2019
Keywords provided by Maria Helena Santa-Clara Pombo Rodrigues, University of Lisbon:
Exercise training
Cardiac resynchronization therapy
Autonomic nervous system modulation
Chronic Heart failure
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Failure
Heart Diseases
Cardiovascular Diseases