Trial document




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  DRKS00013902

Trial Description

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Title

Natural time course of lung function and respiratory muscle strength in patients with optimally treated stable heart failure with reduced ejection fraction

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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Brief Summary in Scientific Language

Based on clinical and pathophysiological considerations the current heart failure guideline of the European Society of Cardiology (ESC) classifies heart failure (HF) into 3 groups: heart failure with reduced (HFrEF), with midrange (HFmrEF) and with preserved ejection fraction (HFpEF).
While some evidence exists on respiratory muscle dysfunction in HF no study has yet investigated its exact pathophysiological association with left ventricular pump-function. Likewise a use of a comprehensive set of investigations in measuring respiratory muscle strength in heart failure is still lacking.
The present study therefore aims to investigate the pathophysiology of respiratory muscle dysfunction in patients with optimally treated, stable HFrEF by means of multi-modal respiratory and skeletal muscle strength testing (including diaphragm ultrasound, magnetic phrenic nerve Stimulation with assessment of transdiaphragmatic pressures and transdiaphragmatic pressures after a comprehensive set of voluntary tests). That said answers can be given (1) to the question whether respiratory muscle dysfunction contributes to the sensation of breathlesness and/or exercise intolerance independent from left ventricular function in HF. (2) to the question what the natural time course of respiratory muscle dysfunction in these patients looks like.
These novel insights into respiratory muscle dysfunction in HF are planned to build the basis for innovative studies on targeted, nocturnal (for example) mask based therapies of respiratory muscle dysfunction in HF.
This will be done exploratively in 15 well-characterised patients with optimally treated and stable HFrEF. Lung function (incl. respiratory muscle strength) and cardiac function will be measured every 6 months.

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Organizational Data

  •   DRKS00013902
  •   2018/03/20
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  •   yes
  •   Approved
  •   2016-072-f-S, Ethik-Kommission der Ärztekammer Westfalen-Lippe und der med. Fakultät der Westfälischen Wilhelms-Universität Münster
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Secondary IDs

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Health Condition or Problem studied

  •   I50.1 -  Left ventricular failure
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Interventions/Observational Groups

  •   Patients with heart failure with reduced ejection fraction will undergo a comprehensive and unique set of lung function and respiratory muscle strength tests within our lab of respiratory physiology.
    This will be done at daytime.
    Prior to all of this a comprehensive clinical examination, measurement of NT-BNP levels and a current transthoracic echocardiogram will be obtained within a regular clinic appointment with our specialty clinic for heart failure patients at Münster university hospital.
    First of all current symptom scores, a 6 Minute walk distance test including assessment of the sensation of breathlesness and a test of maximal arm and leg strength will be performed.
    Secondly, standard lung function including measurement of vital capacity and FEV1/FVC and standard test of maximal inspiratory and expiratory pressures will be performed.
    Thirdly, comprehensive assessment of diaphragmatic properties using diaphragm ultrasound will be performed.
    Fourthly, intraesophageal and intragastral baloon catheters will be placed in order to continuously record trans-diaphragmatic pressure after magnetic both cortical and cervical phrenic nerve stimulation and after a comprehensive set of voluntary tests with testing of their interaction allowing for measurement of central diaphragmatic fatigue.
    The above mentioned measurements will be performed every 6 months for 18 months after the first measurement (in sum respiratory muscle strength will be measured four times).


  •   Ultimately, 15 control subjects (matched for age and gender; with no abnormal findings in an electrocardiogram, echocardiogram and normal NT-BNP levels) will undergo the study protocol described above.

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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Twitch transdiaphragmatic pressure after magnetic cervical stimulation of the phrenic nerves [cmH2O; measured through intraosophageal and intragastral balloon catheters with pressure recordings in response to bilateral, supramaximal cervical magnetic stimulation]

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Secondary Outcome

Fatigue Severity Scale [points], quality of life using SF-36 [points], six-minute walk distance (6 MWD) [m], Medical Research Council Dyspnoea Scale [points], Borg Dyspnoea Scale pre and post 6 MWD [points],
-> the above mentioned values will be obtained by means of questionaires
leg muscle strength [kg],
-> the above mentioned value will be obtained by means of a dynamometer
Forced vital capacity [ml], FEV1/FVC [%], MIP [cmH2O], MEP [cmH2O], SNIP [cmH2O], peak cough Flow [L/sek],
-> the above mentioned values will be obtained by means of spirometry devices
Rate of rise of diaphramatic amplitude during tidal breathing on ultrasound [cm/sec], Rate of rise of diaphramatic amplitude during Sniff maneuver on ultrasound, Rate of rise of diaphramatic amplitude during maximal inspiration on ultrasound, diaphragm thickness after maximal inspiration on ultrasound [cm], diaphragm thickness after maximal exspiration on ultrasound, diaphragm thickness after tidal breathing on ultrasound [cm], thickening ratio [n.u.],
-> the above mentioned values will be obtained by means of diaphragm ultrasound,
twitch mouth pressure after magnetic cervical stimulation of the phrenic nerves [cmH2O],
twitch mouth pressure after magnetic cortical stimulation of the phrenic nerves [cmH2O],
twitch transdiaphragmatic pressure after magnetic cortical stimulation of the phrenic nerves [cmH2O],
twitch gastric pressure after thoracic magnetic stimulation of the (expiratory) abdominal muscles [cmH2O]
twitch mouth pressure after thoracic magnetic stimulation of the (expiratory) abdominal muscles [cmH2O]
phrenic nerve conduction time after cortical magentic stimulation [ms], phrenic nerve conduction time after cervical magentic stimulation [ms], Amplitude of compound diaphragm muscle action potential after cortical magentic stimulation [mA], Amplitude of compound diaphragm muscle action potential after cervical magnetic stimulation [mA], central motor conduction time [ms],
transdiaphragmatic pressure after voluntary maneuvers [cmH2O], mouth pressure after voluntary maneuvers [cmH20], Releaxation-rate of Twitch transdiaphragmatic pressure after magnetic cervical stimulation of the phrenic nerves [msec],
The above mentioned values will be obtained through intraosophageal and intragastral balloon catheters with pressure recordings in response to bilateral, supramaximal cervical and cortical magnetic stimulation as well as to a set of voluntary breathing maneuvers. Plus, compound muscle Action potential in response to magnetic Stimulation will be recorded through surface electrodes and be analysed in terms of both its onset latency and its Amplitude.
Releaxation-rate of Twitch transdiaphragmatic pressure after magnetic cervical stimulation of the phrenic nerves [msec]

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2018/07/01
  •   30
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

a. Age > 18 years (no age limit)
b. able to consent
c. Diagnosis of heart failure with reduced ejection fraction -HFrEF- according to the most recent Guidelines of the European Society of Cardiology (ESC); >12 weeks since the diagnosis of HFrEF has been made; no hospitalisation for HF in the last 4 weeks; optimal medical therapy in accordance with the most recent Guidelines of the European Society of Cardiology (ESC) with no change in medication in the last 4 weeks and combination therapy for HFrEF -where there was no treatment with beta blockers or ACE Inhibitors/ARBs in HFrEF, then the reason must be documented-
d. Controls (matched for age and gender) with normal findings on echocardiogram, electrocardiogram and normal levels of natriuretic peptide hormone

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Exclusion Criteria

- Body Mass Index (BMI) > 35
- Chronic obstructive pulmonary disease, emphysema
- Presence of severe neurological comorbidities especially primary myopathy, muscular dystrophy, motor neuron disease, phrenic nerve disease, epilepsy, multiple sclerosis, parkinson’s disease
- Severe psychiatric disease including dementia
- Thoracic wall disease
- Cardiac pacemaker

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Addresses

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    • Department für Neurologie - Klinik für Schlafmedizin und neuromuskuläre Erkrankungen Universitätsklinikum Münster
    • Albert-Schweitzer-Campus 1
    • 48149  Münster
    • Germany
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    • Klinik für angeborene (EMAH) und erworbene Herzfehler Universitätsklinikum Münster
    • Mr.  Prof. Dr. Dr.  Paul-Gerhard  Diller 
    • Albert-Schweitzer-Campus 1
    • 48149  Münster
    • Germany
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    • Department für Neurologie- Klinik für Schlafmedizin und neuromuskuläre Erkrankungen Universitätsklinikum Münster
    • Mr.  Dr. med.  Matthias  Boentert 
    • Albert-Schweitzer-Campus 1
    • 48149  Münster
    • Germany
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    • Department für Kardiologie
    • Mr.  Univ.-Prof. Dr. med.  Ali  Yilmaz 
    • Albert-Schweitzer-Campus 1
    • 48149  Münster
    • Germany
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    • Department für Kardiologie
    • Mr.  Christian  Pogoda 
    • Albert-Schweitzer-Campus 1
    • 48149  Münster
    • Germany
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    • Clemens Hospital Münster
    • Mr.  Prof. Dr.  Olaf  Oldenburg 
    • Düesbergweg 124
    • 48153  Münster
    • Germany
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    • Cardiovascular Medicine DivisionFondazione Toscana Gabriele Monasterio and Institute of Life Sciences at Sant Anna School of Advanced Studies
    • Mr.  Prof. Dr.  Michele  Emdin 
    • via Giuseppe Moruzzi 1
    • 56124  Pisa
    • Italy
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    • Cardiovascular Medicine DivisionFondazione Toscana Gabriele Monasterio
    • Mr.  Dr.  Alberto  Giannoni 
    • via Giuseppe Moruzzi 1
    • 56124  Pisa
    • Italy
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    • Department für Neurologie - Klinik für Schlafmedizin und neuromuskuläre Erkrankungen Universitätsklinikum Münster
    • Mr.  Herr  Jens  Spiesshoefer 
    • Albert-Schweitzer-Campus 1
    • 48149  Münster
    • Germany
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    • Department für Neurologie- Klinik für Schlafmedizin und neuromuskuläre Erkrankungen Universitätsklinikum Münster
    • Mr.  Dr. med.  Matthias  Boentert 
    • Albert-Schweitzer-Campus 1
    • 48149  Münster
    • Germany
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Sources of Monetary or Material Support

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    • Department für Neurologie - Klinik für Schlafmedizin und neuromuskuläre Erkrankungen Universitätsklinikum Münster
    • Albert-Schweitzer-Campus 1
    • 48149  Münster
    • Germany
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Status

  •   Recruiting stopped after recruiting started
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Trial Publications, Results and other Documents

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