Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of HFpEF (TRAINING-HF)

May 17, 2017 updated by: Universitat Jaume I

Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction

Heart failure (HF) with preserved ejection fraction (HFpEF) has become the most prevalent form of HF in developed countries. Despite its increasing in prevalence, there is no evidence-based effective therapy for HFpEF The purpose of this study was to evaluate whether inspiratory muscle training (IMT), functional electrical stimulation (FES), or combination of both improve exercise capacity as well as left ventricular diastolic function, biomarkers' profile, quality of life (QoL) and prognosis in patients with HFpEF.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study was designed as a prospective, controlled, randomized, four-armed, efficacy trial of patients with the diagnosis of HFpEF and New York Heart Association functional class II-III/IV, diagnosed according to criteria of the European Society of Cardiology. A computer-generated randomization scheme was used to allocate participants (in a 1:1:1:1 ratio) to receive: 1) a home-based 12-week program of inspiratory muscle training (IMT) or; 2) a 12-week program of functional electrical stimulation (FES) of lower limb muscles or; 3) standard treatment (ST) alone or; 4) combination of IMT and FES. The study is being conducted in a single center in Spain. Independently of staggered entry, the minimum duration of a patient's participation is 6 months (from first to last visit). All patients will provide signed informed consent and the protocol has been approved by the research ethics committee of our center in accordance with the principles of the Declaration of Helsinki and national regulations.

Study population Candidate patients are selected from the outpatient's clinics of HF of the Hospital Clínico Universitario of Valencia.

Study objectives The primary endpoint of the study is a clinical endpoint of three and six months change in peak oxygen uptake (peak VO2).

Secondary endpoints are three and six month changes in echocardiogram parameters, QoL and prognostic biomarkers. The investigators also will specifically focus on number of episodes of worsening HF at 6 months:

  1. Change in E/e' after three and six months.
  2. Change in left atrial volume index after three and six months.
  3. Change in health-related QoL measured by the Minnesota Living With Heart Failure Questionnaire (MLHF) after three and six months.
  4. Change in natriuretic peptide (NT-proBNP) after three and six months.
  5. Change in minute ventilation/carbon dioxide production (VE/VCO2) slope after three and six months.
  6. Number of episodes of acute HF hospitalizations and number of episodes of worsening HF not requiring hospitalization at 6 months.

Intervention

Eligibility assessment and screening visit After reviewing the inclusion/exclusion criteria and signing the informed consent form, a comprehensive medical history, physical examination, anthropometry and examination tests will be performed. The examination tests include: electrocardiogram (ECG) echocardiography, cardiopulmonary exercise testing (CPET), 6-minute walk test (6-MWT), inspiratory muscle function test, QoL assessment by the Minnesota Living With Heart Failure Questionnaire (MLHF) and blood samples for a panel of baseline biomarkers.

Finally, patients are randomized (1:1:1:1) to four groups: 1) ST alone or; 2) a home-based 12-week program of IMT or; 3) a 12-week program of FES or; 4) combination of IMT and FES (IMT+FES) during 12 weeks.

12-week and six months visits All patients will be evaluated after 12-week supervised training, and six months after randomization. Evaluation will include medical history, physical examination, anthropometry and functional and QoL assessment tests (ECG, CPET, 6-MWT, inspiratory muscle function test, MLHF and blood tests).

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Previous history of symptomatic heart failure NYHA (New York Heart Association )functional class ≥II with Normal left ventricular ejection fraction:

    • ejection fraction >0.50 by Simpson method
    • end-diastolic diameter <60 mm

  • Structural heart disease:

    • left ventricle hypertrophy/left atrial enlargement and/or
    • diastolic dysfunction estimated by 2D echocardiography
  • Previous admission for acute heart failure
  • Clinical stability, without hospital admissions in the past 3 month

Exclusion Criteria:

  • Perform a valid baseline exercise test
  • Significant primary moderate to severe valvular disease
  • Acute coronary syndrome or cardiac surgery within the previous three months
  • Signs of ischemia during cardiopulmonary exercise testing
  • Significant primary pulmonary disease; including pulmonary arterial hypertension, chronic thromboembolic pulmonary disease or chronic obstructive pulmonary disease
  • Any other comorbidity with an expectancy of life less than one year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Standard treatment
Only standard medical treatment
Other: Standard treatment
Patients allocated to this arm will not receive any physical therapy, only standard medical treatment. They will be checked weekly by a physiotherapist who measures their maximal inspiratory mouth pressure each time.
Active Comparator: IMT group
Standard medical treatment associated to Inspiratory muscle training
Other: IMT
Patients allocated to IMT arm will receive standard medical treatment and will be instructed to train at home twice daily, for 20 minutes each session, and during 12 weeks using a threshold inspiratory muscle trainer (Threshold IMT®, Respironics Inc.). All of them will be instructed by a respiratory therapist and educated to maintain a diaphragmatic breathing during the training period. The subjects start breathing at a resistance equal to 25-30% of their maximal inspiratory pressure (MIP) for 1 week. The respiratory therapist examines the patients at weekly intervals by checking the diary card and measuring their MIP each time. The resistance is modified each session according to their 25-30% of their MIP measured.
Other Names:
  • Inspiratory muscular training
Active Comparator: FES group
Standard medical treatment associated to functional electrostimulation of both legs for 45 minutes a day, 2 days per week for a total of 12 weeks.
Other: FES
Patients allocated to FES arm will receive standard medical treatment and will be trained in a FES program of both legs by a physiotherapist for 45 minutes a day, 2 days per week for a total of 12 weeks. Eight adhesive electrodes are positioned on the skin over the quadriceps and gastrocnemius muscles of both legs. The stimulator is configured to deliver a direct electrical current at 25 Hz for 5 seconds followed by a 5-second rest. The intensity of the stimulation is adjusted to achieve a visible muscle contraction without discomfort.
Other Names:
  • Functional electrostimulation of lower limbs
Active Comparator: IMT+FES group
Standard medical treatment associated to combination of inspiratory muscle training and functional electrostimulation of both legs
Other: IMT
Patients allocated to IMT arm will receive standard medical treatment and will be instructed to train at home twice daily, for 20 minutes each session, and during 12 weeks using a threshold inspiratory muscle trainer (Threshold IMT®, Respironics Inc.). All of them will be instructed by a respiratory therapist and educated to maintain a diaphragmatic breathing during the training period. The subjects start breathing at a resistance equal to 25-30% of their maximal inspiratory pressure (MIP) for 1 week. The respiratory therapist examines the patients at weekly intervals by checking the diary card and measuring their MIP each time. The resistance is modified each session according to their 25-30% of their MIP measured.
Other Names:
  • Inspiratory muscular training
Other: FES
Patients allocated to FES arm will receive standard medical treatment and will be trained in a FES program of both legs by a physiotherapist for 45 minutes a day, 2 days per week for a total of 12 weeks. Eight adhesive electrodes are positioned on the skin over the quadriceps and gastrocnemius muscles of both legs. The stimulator is configured to deliver a direct electrical current at 25 Hz for 5 seconds followed by a 5-second rest. The intensity of the stimulation is adjusted to achieve a visible muscle contraction without discomfort.
Other Names:
  • Functional electrostimulation of lower limbs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional capacity measured as peak oxygen uptake (peak VO2) in ml/min/kg .
Time Frame: changes at 12 weeks and 6 months

Maximal functional capacity will be evaluated with an incremental and symptom-limited cardiopulmonary exercise testing (CORTEX Metamax 3B) on a bicycle ergometer, beginning with a workload of 10 W and increasing stepwise at 10-W increments every 1 min. During exercise, patients were continuously monitored with twelve-lead electrocardiogram and blood pressure measurements every 2 min. Gas exchange data and cardiopulmonary variables were averaged every 10 seconds values. Peak VO2 is considered the highest value of VO2 during the last 20 s of exercise.

The improvement > of 10% in peak VO2 will be considered clinically meaningful
changes at 12 weeks and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional capacity measured as distance walked in 6 minutes
Time Frame: changes at 12 weeks and 6 months
Patients will be instructed to cover the maximum distance (meters) possible in six minutes, at a self-graded walking speed, pausing to rest when needed. Each subject will undergo 4 tests. The goal of the first one was to allow the patient to familiarize with the test.
changes at 12 weeks and 6 months
Change in echocardiographic parameter of diastolic disfunction: e' septal (cm/s)
Time Frame: changes in rest at 12 weeks and 6 months

Doppler echocardiogram examination of e' septal (cm/s) will be performed under resting conditions using 2D echocardiography (iE33, Philips). e' septal (cm/s) parameter will be measured according to current guidelines of the European Society of Echocardiography:

Only significant improvements in this parameter will be considered
changes in rest at 12 weeks and 6 months
Change in echocardiographic parameter of diastolic disfunction: left atrial volume index (mm/m2)
Time Frame: changes in rest at 12 weeks and 6 months

Doppler echocardiogram examination of left atrial volume index (mm/m2) will be performed under resting conditions using 2D echocardiography (iE33, Philips). Left atrial volume index (mm/m2) will be measured according to current guidelines of the European Society of Echocardiography.

Only significant improvements in this parameter will be considered
changes in rest at 12 weeks and 6 months
Change in echocardiographic parameter of diastolic disfunction: E/e' ratio
Time Frame: changes in rest at 12 weeks and 6 months

Doppler echocardiogram examination of E/e' ratio will be performed under resting conditions using 2D echocardiography (iE33, Philips). E/e' ratio parameter will be measured according to current guidelines of the European Society of Echocardiography.

Only significant improvement in this parameter will be considered
changes in rest at 12 weeks and 6 months
Change in health-related QoL
Time Frame: changes at 12 weeks and 6 months
Change in health-related QoL will be measured by the Minnesota Living With Heart Failure Questionnaire (no units) Only significant improvements in these parameters will be considered
changes at 12 weeks and 6 months
Number of rehospitalizations or worsening HF at 6 months
Time Frame: changes at 6 months
Number of episodes of acute HF hospitalizations and number of episodes of worsening HF not requiring hospitalization at 6 months among different arms.
changes at 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitat Jaume I

Collaborators

INCLIVA
Hospital Clínico Universitario de Valencia

Investigators

  • Principal Investigator: Patricia Palau, M.D., PhD, Universitat Jaume I
  • Study Director: Eloy Domínguez, M.D, Universitat Jaume I
  • Study Chair: Julio Núñez, M.D., PhD, Universitat de Valencia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

December 1, 2015

First Submitted That Met QC Criteria

December 22, 2015

First Posted (Estimate)

December 23, 2015

Study Record Updates

Last Update Posted (Actual)

May 18, 2017

Last Update Submitted That Met QC Criteria

May 17, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMT-FES 01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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