<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03032562</url>
  </required_header>
  <id_info>
    <org_study_id>KSN_2016_2_MB</org_study_id>
    <nct_id>NCT03032562</nct_id>
  </id_info>
  <brief_title>Respiratory Muscle Strength and Function in Neuromuscular Disorders and Chronic Obstructive Pulmonary Disease</brief_title>
  <official_title>Multimodal Measurement of Respiratory Muscle Strength and Function: Validation of Volitional and Non-volitional Tests With Regard to Nocturnal Hypoventilation in Patients With Neuromuscular Disorders and Chronic Obstructive Pulmonary Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Westfälische Wilhelms-Universität Münster</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Westfälische Wilhelms-Universität Münster</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Using an extensive set of both volitional and non-volitional tests of respiratory muscle&#xD;
      function and strength it is the aim of this study to&#xD;
&#xD;
        -  identify disease-specific patterns of respiratory muscle impairment in different NMD and&#xD;
           COPD&#xD;
&#xD;
        -  establish which set of tests is predictive of sleep-disordered breathing or daytime&#xD;
           hypercapnia in patients with NMD or COPD, respectively.&#xD;
&#xD;
        -  to investigate the decline of respiratory muscle function in patients with progressive&#xD;
           NMD and COPD along with sleep studies and capnography&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Numerous neuromuscular disorders (NMD) are characterized not only by weakness of axial and&#xD;
      limb muscles but also by respiratory muscle and upper airway involvement. Respiratory muscle&#xD;
      weakness first manifests as sleep-disordered breathing (SDB). SDB in neuromuscular disease&#xD;
      mainly comprises alveolar hypoventilation but upper airway collapse may also occur because&#xD;
      pharyngeal muscle tone is impaired by both neuromuscular weakness and sleep.&#xD;
&#xD;
      Diaphragmatic weakness and myopathy are hallmarks of advanced obstructive pulmonary disease&#xD;
      leading to even greater impairment of gas exchange in affected patients.&#xD;
&#xD;
      Non-invasive ventilation (NIV) should be initiated in patients with diaphragm weakness if&#xD;
      significant SDB or hypercapnic respiratory failure is present. Indication criteria for NIV&#xD;
      include measurement of spiromanometric parameters such as forced vital capacity (FVC),&#xD;
      maximum inspiratory pressure (MIP), or sniff nasal inspiratory pressure (SNIP). These&#xD;
      measurements are volitional, i. e. test results are dependent on individual patient effort&#xD;
      and may show intraindividual variance which may not properly reflect disease progression or&#xD;
      treatment effects, respectively. Associations between volitional and non-volitional methods&#xD;
      of respiratory muscle strength testing have been reported mainly for healthy individuals but&#xD;
      only scarcely in patients with specific NMD.&#xD;
&#xD;
      Non-volitional tests of respiratory muscle strength include phrenic nerve conduction studies,&#xD;
      diaphragmatic ultrasound, and magnetic stimulation of the phrenic nerves in particular.&#xD;
      Magnetic stimulation is usually combined with esophageal and gastric manometry yielding the&#xD;
      twitch transdiaphragmatic pressure which closely reflects diaphragmatic strength.&#xD;
&#xD;
      It is desirable to obtain validated data on both volitional and non-volitional tests of&#xD;
      respiratory muscle strength in various NMD. Validation has to be carried out with regard to&#xD;
      both daytime hypercapnia and nocturnal retention of carbon dioxide because the latter often&#xD;
      represents the earliest manifestation of respiratory muscle weakness. SDB often starts long&#xD;
      before exertional dyspnea or orthopnea develop. Since NIV is one of the mainstays of&#xD;
      symptomatic treatment in both NMD and advanced obstructive lung disease, early recognition of&#xD;
      SDB is crucial for optimal patient care, and in many conditions, life expectancy and quality&#xD;
      of life may be substantially increased by NIV. In this study, FVC, MIP, MEP and SNIP testing&#xD;
      along with non-volitional methods and diaphragmatic ultrasound will be applied in order to&#xD;
      establish a protocol which may help to reliably predict SDB or need for ventilatory support,&#xD;
      respectively.&#xD;
&#xD;
      Patients with chronic obstructive pulmonary disease (COPD) develop flattening, shortening,&#xD;
      and weakness of the diaphragm. This is not only due to downward dislocation of the diaphragm&#xD;
      but also to impairment of contractile function, tissue structure, and intracellular&#xD;
      biochemistry. Respiratory muscle weakness in COPD is of major clinical relevance since&#xD;
      maximum inspiratory pressure is an independent predictor of survival in severely affected&#xD;
      patients. In addition, hypercapnic respiratory failure due to inspiratory muscle weakness is&#xD;
      associated with morbidity and mortality in COPD.&#xD;
&#xD;
      Direct comparison of both volitional and non-volitional measures of respiratory muscle&#xD;
      function between patients with diaphragmatic weakness due to neuromuscular disease and&#xD;
      patients with COPD is desirable. This approach may allow for further characterization of&#xD;
      &quot;impairment patterns&quot; probably specific to either COPD or certain neuromuscular disease,&#xD;
      respectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 1, 2016</start_date>
  <completion_date type="Anticipated">February 28, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Presence of daytime hypercapnia</measure>
    <time_frame>1 day</time_frame>
    <description>paCO2 &gt; 45 mmHg</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Presence of sleep-disordered breathing</measure>
    <time_frame>1 day</time_frame>
    <description>nocturnal tcCO2 &gt; 50 mmHg, delta tcCO2 &gt; 10 mmHg</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>twitch transdiaphragmatic pressure</measure>
    <time_frame>1 day</time_frame>
    <description>difference between intraesophageal and intragastral pressure after posterior magnetic stimulation of the phrenic nerves</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Respiratory Muscle Paralysis</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <description>Patients with neuromuscular disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2</arm_group_label>
    <description>Patients with chronic obstructive pulmonary disease</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Multimodal measurement of respiratory muscle function and strength</intervention_name>
    <description>Sleep-studies, capnography, spiromanometry, phrenic nerve conduction studies, magnetic phrenic nerve stimulation, diaphragmatic ultrasound</description>
    <arm_group_label>1</arm_group_label>
    <arm_group_label>2</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with known neuromuscular disease and individuals with chronic obstructive&#xD;
        pulmonary disease (and no neuromuscular disorder)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with NMD (n=100): Amyotrophic lateral sclerosis, Pompe's disease, myotonic&#xD;
             dystrophy type 1, limb-girdle muscular dystrophies, spinal muscular atrophy, etc.&#xD;
&#xD;
          -  patients with chronic obstructive lung disease (n=100)&#xD;
&#xD;
          -  age 18 - 80 years&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  significant chest wall deformity&#xD;
&#xD;
          -  tracheostomy&#xD;
&#xD;
          -  inability to sit in the upright position&#xD;
&#xD;
          -  impaired consciousness&#xD;
&#xD;
          -  acute or severe medical comorbidity&#xD;
&#xD;
          -  mechanical ventilation for more than 4 hours during daytime&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>Matthias Boentert, MD</last_name>
    <phone>+49-251-83</phone>
    <phone_ext>44458</phone_ext>
    <email>matthias.boentert@ukmuenster.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Peter Young, MD</last_name>
    <phone>+49-251-83</phone>
    <phone_ext>48196</phone_ext>
    <email>peter.young@ukmuenster.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital Münster, Department of Sleep Medicine and Neuromuscular Disorders</name>
      <address>
        <city>Munster</city>
        <state>NRW</state>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matthias Boentert, MD</last_name>
      <phone>+49-251-83</phone>
      <phone_ext>44458</phone_ext>
      <email>matthias.boentert@ukmuenster.de</email>
    </contact>
    <investigator>
      <last_name>Matthias Boentert, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Bethanien Hospital</name>
      <address>
        <city>Solingen</city>
        <state>NRW</state>
        <zip>42699</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Winfried Randerath, MD</last_name>
      <phone>+49-212</phone>
      <phone_ext>636000</phone_ext>
      <email>winfried.randerath@klinik-bethanien.de</email>
    </contact>
    <contact_backup>
      <last_name>Simon Herkenrath, MD</last_name>
      <phone>+49-212</phone>
      <phone_ext>636000</phone_ext>
      <email>simon-dominik.herkenrath@klinik-bethanien.de</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>January 25, 2017</last_update_submitted>
  <last_update_submitted_qc>January 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Westfälische Wilhelms-Universität Münster</investigator_affiliation>
    <investigator_full_name>Matthias Boentert</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>respiratory muscle strength</keyword>
  <keyword>sleep-disordered breathing</keyword>
  <keyword>neuromuscular disease</keyword>
  <keyword>chronic-obstructive pulmonary disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <mesh_term>Respiratory Paralysis</mesh_term>
    <mesh_term>Paralysis</mesh_term>
    <mesh_term>Neuromuscular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03032562
org study id: KSN_2016_2_MB
nct id: NCT03032562
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Using an extensive set of both volitional and non-volitional tests of respiratory muscle
      function and strength it is the aim of this study to

        -  identify disease-specific patterns of respiratory muscle impairment in different NMD and
           COPD

        -  establish which set of tests is predictive of sleep-disordered breathing or daytime
           hypercapnia in patients with NMD or COPD, respectively.

        -  to investigate the decline of respiratory muscle function in patients with progressive
           NMD and COPD along with sleep studies and capnography
Numerous neuromuscular disorders (NMD) are characterized not only by weakness of axial and
      limb muscles but also by respiratory muscle and upper airway involvement. Respiratory muscle
      weakness first manifests as sleep-disordered breathing (SDB). SDB in neuromuscular disease
      mainly comprises alveolar hypoventilation but upper airway collapse may also occur because
      pharyngeal muscle tone is impaired by both neuromuscular weakness and sleep.

      Diaphragmatic weakness and myopathy are hallmarks of advanced obstructive pulmonary disease
      leading to even greater impairment of gas exchange in affected patients.

      Non-invasive ventilation (NIV) should be initiated in patients with diaphragm weakness if
      significant SDB or hypercapnic respiratory failure is present. Indication criteria for NIV
      include measurement of spiromanometric parameters such as forced vital capacity (FVC),
      maximum inspiratory pressure (MIP), or sniff nasal inspiratory pressure (SNIP). These
      measurements are volitional, i. e. test results are dependent on individual patient effort
      and may show intraindividual variance which may not properly reflect disease progression or
      treatment effects, respectively. Associations between volitional and non-volitional methods
      of respiratory muscle strength testing have been reported mainly for healthy individuals but
      only scarcely in patients with specific NMD.

      Non-volitional tests of respiratory muscle strength include phrenic nerve conduction studies,
      diaphragmatic ultrasound, and magnetic stimulation of the phrenic nerves in particular.
      Magnetic stimulation is usually combined with esophageal and gastric manometry yielding the
      twitch transdiaphragmatic pressure which closely reflects diaphragmatic strength.

      It is desirable to obtain validated data on both volitional and non-volitional tests of
      respiratory muscle strength in various NMD. Validation has to be carried out with regard to
      both daytime hypercapnia and nocturnal retention of carbon dioxide because the latter often
      represents the earliest manifestation of respiratory muscle weakness. SDB often starts long
      before exertional dyspnea or orthopnea develop. Since NIV is one of the mainstays of
      symptomatic treatment in both NMD and advanced obstructive lung disease, early recognition of
      SDB is crucial for optimal patient care, and in many conditions, life expectancy and quality
      of life may be substantially increased by NIV. In this study, FVC, MIP, MEP and SNIP testing
      along with non-volitional methods and diaphragmatic ultrasound will be applied in order to
      establish a protocol which may help to reliably predict SDB or need for ventilatory support,
      respectively.

      Patients with chronic obstructive pulmonary disease (COPD) develop flattening, shortening,
      and weakness of the diaphragm. This is not only due to downward dislocation of the diaphragm
      but also to impairment of contractile function, tissue structure, and intracellular
      biochemistry. Respiratory muscle weakness in COPD is of major clinical relevance since
      maximum inspiratory pressure is an independent predictor of survival in severely affected
      patients. In addition, hypercapnic respiratory failure due to inspiratory muscle weakness is
      associated with morbidity and mortality in COPD.

      Direct comparison of both volitional and non-volitional measures of respiratory muscle
      function between patients with diaphragmatic weakness due to neuromuscular disease and
      patients with COPD is desirable. This approach may allow for further characterization of
      "impairment patterns" probably specific to either COPD or certain neuromuscular disease,
      respectively.
observational model: Cohort
time perspective: Prospective
measure: Presence of daytime hypercapnia
time frame: 1 day
description: paCO2 > 45 mmHg
measure: Presence of sleep-disordered breathing
time frame: 1 day
description: nocturnal tcCO2 > 50 mmHg, delta tcCO2 > 10 mmHg
measure: twitch transdiaphragmatic pressure
time frame: 1 day
description: difference between intraesophageal and intragastral pressure after posterior magnetic stimulation of the phrenic nerves
arm group label: 1
description: Patients with neuromuscular disease
arm group label: 2
description: Patients with chronic obstructive pulmonary disease
intervention type: Diagnostic Test
intervention name: Multimodal measurement of respiratory muscle function and strength
description: Sleep-studies, capnography, spiromanometry, phrenic nerve conduction studies, magnetic phrenic nerve stimulation, diaphragmatic ultrasound
arm group label: 1
arm group label: 2
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
last name: Matthias Boentert, MD
phone: +49-251-83
phone ext: 44458
email: matthias.boentert@ukmuenster.de
last name: Peter Young, MD
phone: +49-251-83
phone ext: 48196
email: peter.young@ukmuenster.de
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Westfälische Wilhelms-Universität Münster
investigator full name: Matthias Boentert
investigator title: MD
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Respiratory Paralysis
mesh term: Paralysis
mesh term: Neuromuscular Diseases
sharing ipd: No