<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/NCT04430686</url>
  </required_header>
  <id_info>
    <org_study_id>REC:20/L0/0275</org_study_id>
    <nct_id>NCT04430686</nct_id>
  </id_info>
  <brief_title>Respiratory Complications in ALS</brief_title>
  <official_title>Respiratory Complications Associated With ALS and Their Treatments</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Liverpool University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Liverpool University Hospitals NHS Foundation Trust</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>
      Respiratory failure is the leading cause of death in motor neuron disease (MND) patients.&#xD;
      Symptoms of respiratory dysfunction in MND patients include sleep disturbance, excessive&#xD;
      daytime somnolence, morning headaches and cognitive changes. Almost all MND patients will&#xD;
      develop respiratory problems during the course of their disease. In a small percentage of MND&#xD;
      patients, respiratory failure may present as the primary symptom at onset, whereas more&#xD;
      commonly it develops later in the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Respiratory failure is the leading cause of death in motor neuron disease (MND) patients.&#xD;
      Symptoms of respiratory dysfunction in MND patients include sleep disturbance, excessive&#xD;
      daytime somnolence, morning headaches and cognitive changes. Almost all MND patients will&#xD;
      develop respiratory problems during the course of their disease. In a small percentage of MND&#xD;
      patients, respiratory failure may present as the primary symptom at onset, whereas more&#xD;
      commonly it develops later in the disease. (1) Forced vital capacity (FVC), taken either&#xD;
      supine or erect, is the most commonly used measurement tool of respiratory function. Such&#xD;
      measures are well recognized predictors of survival (2), with supine FVC a more accurate&#xD;
      marker of diaphragmatic weakness (1). However, FVC may not be sensitive for the detection of&#xD;
      early respiratory failure and can be technically difficult to perform in patients with severe&#xD;
      bulbar weakness (3). Other respiratory measures include maximal inspiratory pressure (MIP),&#xD;
      maximal expiratory pressure (MEP), sniff nasal inspiratory pressure (SNIP) and, less&#xD;
      commonly, formal assessment of arterial blood gases (ABG). Interpretation of the trends of&#xD;
      these measures over time, combined with the clinical picture, determines appropriate&#xD;
      respiratory management. Significantly, the advent of non-invasive ventilation (NIV) has&#xD;
      provided clear benefit in terms of improving symptoms, QOL and prolonging survival by up to 7&#xD;
      months in MND patients, making NIV a central armamentarium of respiratory management in these&#xD;
      patients (4) Bilevel ventilation devices (Bi-PAP) are most commonly used as initial therapy.&#xD;
      There are no established evidence-based guidelines regarding optimal timing for initiation of&#xD;
      NIV.Some studies suggest that an early introduction of NIV may increase survival (5), reduce&#xD;
      respiratory-related energy expenditure (6) and improve adherence to therapy and QOL (7).Once&#xD;
      initiated, poor optimisation of NIV represents an independent risk factor for mortality (8)&#xD;
      However, there are no randomized control trial data available that have compared the specific&#xD;
      parameters of bilevel modes of ventilation across various patient cohorts. Different&#xD;
      strategies have been used to optimize patient comfort, including adjusting the type of mask&#xD;
      and fittings, providing humidified air and testing different Bi-PAP pressure settings.&#xD;
      Despite these measures, up to 30% of MND patients cannot tolerate therapy due to secondary&#xD;
      effects of anxiety, emotional lability from pseudobulbar palsy, excessive salivation,&#xD;
      claustrophobia and nasal bridge soreness (8) Importantly, the key factors that affect overall&#xD;
      compliance with this treatment are the presence of bulbar dysfunction with bulbar onset&#xD;
      patients six times less likely to tolerate NIV than those with limb onset disease (9) Future&#xD;
      efforts must be focused on determining more accurate testing for early respiratory failure,&#xD;
      optimal time to initiate NIV and the comfortable adaptation of NIV devices for patients with&#xD;
      bulbar weakness&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Actual">September 1, 2021</completion_date>
  <primary_completion_date type="Actual">September 1, 2021</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival after initiation of assisted ventilation</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival at one month and six months or longer</measure>
    <time_frame>1 month and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life assessed using validated health status questionnaires</measure>
    <time_frame>1 year</time_frame>
    <description>Any validated functional rating scale, such as the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) or the ALSFRS-Revised (if available)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of initiation of diagnosis of MND and initiation of NIV</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">300</enrollment>
  <condition>Motor Neuron Disease</condition>
  <condition>Pneumonia</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionaires</intervention_name>
    <description>Any validated functional rating scale, such as the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) or the ALSFRS-Revised (if available)</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patient population with ALS&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with ALS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>LiverpoolUHNHS</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>September 21, 2021</last_update_submitted>
  <last_update_submitted_qc>September 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We will make the research available to any MND researchers/patients</ipd_description>
  </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/NCT04430686
org study id: REC:20/L0/0275
nct id: NCT04430686
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Respiratory failure is the leading cause of death in motor neuron disease (MND) patients.
      Symptoms of respiratory dysfunction in MND patients include sleep disturbance, excessive
      daytime somnolence, morning headaches and cognitive changes. Almost all MND patients will
      develop respiratory problems during the course of their disease. In a small percentage of MND
      patients, respiratory failure may present as the primary symptom at onset, whereas more
      commonly it develops later in the disease.
Respiratory failure is the leading cause of death in motor neuron disease (MND) patients.
      Symptoms of respiratory dysfunction in MND patients include sleep disturbance, excessive
      daytime somnolence, morning headaches and cognitive changes. Almost all MND patients will
      develop respiratory problems during the course of their disease. In a small percentage of MND
      patients, respiratory failure may present as the primary symptom at onset, whereas more
      commonly it develops later in the disease. (1) Forced vital capacity (FVC), taken either
      supine or erect, is the most commonly used measurement tool of respiratory function. Such
      measures are well recognized predictors of survival (2), with supine FVC a more accurate
      marker of diaphragmatic weakness (1). However, FVC may not be sensitive for the detection of
      early respiratory failure and can be technically difficult to perform in patients with severe
      bulbar weakness (3). Other respiratory measures include maximal inspiratory pressure (MIP),
      maximal expiratory pressure (MEP), sniff nasal inspiratory pressure (SNIP) and, less
      commonly, formal assessment of arterial blood gases (ABG). Interpretation of the trends of
      these measures over time, combined with the clinical picture, determines appropriate
      respiratory management. Significantly, the advent of non-invasive ventilation (NIV) has
      provided clear benefit in terms of improving symptoms, QOL and prolonging survival by up to 7
      months in MND patients, making NIV a central armamentarium of respiratory management in these
      patients (4) Bilevel ventilation devices (Bi-PAP) are most commonly used as initial therapy.
      There are no established evidence-based guidelines regarding optimal timing for initiation of
      NIV.Some studies suggest that an early introduction of NIV may increase survival (5), reduce
      respiratory-related energy expenditure (6) and improve adherence to therapy and QOL (7).Once
      initiated, poor optimisation of NIV represents an independent risk factor for mortality (8)
      However, there are no randomized control trial data available that have compared the specific
      parameters of bilevel modes of ventilation across various patient cohorts. Different
      strategies have been used to optimize patient comfort, including adjusting the type of mask
      and fittings, providing humidified air and testing different Bi-PAP pressure settings.
      Despite these measures, up to 30% of MND patients cannot tolerate therapy due to secondary
      effects of anxiety, emotional lability from pseudobulbar palsy, excessive salivation,
      claustrophobia and nasal bridge soreness (8) Importantly, the key factors that affect overall
      compliance with this treatment are the presence of bulbar dysfunction with bulbar onset
      patients six times less likely to tolerate NIV than those with limb onset disease (9) Future
      efforts must be focused on determining more accurate testing for early respiratory failure,
      optimal time to initiate NIV and the comfortable adaptation of NIV devices for patients with
      bulbar weakness
observational model: Cohort
time perspective: Retrospective
measure: Overall survival after initiation of assisted ventilation
time frame: 1 year
measure: Survival at one month and six months or longer
time frame: 1 month and 6 months
measure: Quality of life assessed using validated health status questionnaires
time frame: 1 year
description: Any validated functional rating scale, such as the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) or the ALSFRS-Revised (if available)
measure: Time of initiation of diagnosis of MND and initiation of NIV
time frame: 1 year
intervention type: Other
intervention name: Questionaires
description: Any validated functional rating scale, such as the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) or the ALSFRS-Revised (if available)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
sharing ipd: No
ipd description: We will make the research available to any MND researchers/patients