<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/NCT03021252</url>
  </required_header>
  <id_info>
    <org_study_id>PSM/RHB/NR21</org_study_id>
    <nct_id>NCT03021252</nct_id>
  </id_info>
  <brief_title>Respiratory Muscle Training in Stroke Swallowing Disorders</brief_title>
  <acronym>RETORNUS-2</acronym>
  <official_title>The RETORNUS-2 Study: Impact of Respiratory Muscle Training on Swallowing Disorders in Stroke Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Parc de Salut Mar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Instituto de Salud Carlos III</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Parc de Salut Mar</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>
      Clinical randomized clinical trial to assess the effectiveness of incorporating inspiratory&#xD;
      and expiratory muscle training (IEMT) in the rehabilitation of stroke patients with dysphagia&#xD;
      in terms of functional outcomes, comorbidities, survival and quality of life.&#xD;
&#xD;
      This project also incorporates a longitudinal study to assess the clinical impact of&#xD;
      dysphagia on body composition and nutritional status in stroke patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Stroke is a major cause of morbidity and mortality worldwide. Stroke can lead to varying&#xD;
      degrees of oropharyngeal dysphagia (25-85% of patients) and respiratory muscle dysfunction&#xD;
      associated with an increase in medical complications such as bronchoaspiration, malnutrition&#xD;
      and death. Dysphagia is present in a significant proportion of patients admitted to&#xD;
      Rehabilitation (up to 85% depending on series) in stroke. Standard swallow therapy consists&#xD;
      of educational intervention aimed to improve self-management of dysphagia and protect the&#xD;
      airway, oral exercises to improve lingual praxis, and compensatory techniques based on&#xD;
      videofluoroscopic findings. Recent studies suggest that IEMT can improve swallowing efficacy&#xD;
      and reduce eventual bronchoaspiration events.&#xD;
&#xD;
      Nutritional status appears in 9-67% of patients with acute and subacute stroke and has an&#xD;
      impact on functional outcomes and provides information about the risk of hospitalization and&#xD;
      death. Stroke patients are at risk of developing malnutrition because of neurologic&#xD;
      impairments related to feeding (chewing, deglutition and self-feeding) that can result in a&#xD;
      poor food intake. To date, there is only few studies on prevalence and influence of&#xD;
      malnutrition in stroke.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Because of the SARS-COV2 pandemic. Recruitment stopped at 48 patients&#xD;
  </why_stopped>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">September 16, 2020</completion_date>
  <primary_completion_date type="Actual">February 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in respiratory muscle strength</measure>
    <time_frame>Baseline and weekly during 8 weeks</time_frame>
    <description>Respiratory muscle strength is assessed through maximal inspiratory and expiratory pressures (PImax and PEmax, respectively) using a pressure transducer connected to a digital register system. The PImax is measured at mouth during a maximum effort from residual volume against occluded airway. To determine the PEmax, the patients will perform a maximum expiratory effort from total lung capacity (TLC) in the face of the occluded airway. A specific and validated respiratory pressures manometer will be used (Micro RPM, Cardinalhealth, Kent, UK).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in dysphagia severity</measure>
    <time_frame>Baseline, 8 weeks, 6 months post-stroke</time_frame>
    <description>Dysphagia severity is assessed with the Penetration-Aspiration Scale: scores of 1-2 indicate normal swallowing; 3-5, penetration; &gt;6, aspiration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in tongue strength</measure>
    <time_frame>Baseline and weekly during 8 weeks</time_frame>
    <description>Lingual Force (IOPI system): maximum isometric tongue pressure defined as the highest of the three peak isometric tongue pressure scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fat-free mass</measure>
    <time_frame>Baseline, 3 months and 6 months post-stroke</time_frame>
    <description>Fat-free mass measured by electrical bioimpedance in kilograms and expressed as normal, low or high values according to normal values for the reference population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Malnutrition at 6 months</measure>
    <time_frame>Baseline and 6 months post-stroke</time_frame>
    <description>Malnutrition criteria of the European Society of Clinical Nutrition and Metabolism (ESPEN)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Swallowing Disorder</condition>
  <condition>Stroke</condition>
  <condition>Respiratory Muscle Training</condition>
  <condition>Malnutrition</condition>
  <arm_group>
    <arm_group_label>High intensity IEMT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Inspiratory and expiratory muscle training + standard swallow therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham IEMT</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham inspiratory and expiratory muscle training + standard swallow therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>High intensity IEMT</intervention_name>
    <description>Training load will be the maximum inspiratory / expiratory load defined according to patient tolerance equivalent to 10 maximal repetitions (RM) as 10 consecutive inspirations / expirations (x 5 set), three times per day, during 8 weeks. External loads will be increased weekly at intervals of 10 cm H2O as tolerated. Patients will receive standard swallow therapy consisting of swallowing manoeuvres, oral exercises, and compensatory techniques aimed to improve self-management of dysphagia and protect the airway.</description>
    <arm_group_label>High intensity IEMT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham IEMT</intervention_name>
    <description>5 sets of 10 inspirations and expirations in a sham IEMT trainer, three times a day, during 8 weeks.</description>
    <arm_group_label>Sham IEMT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  First-ever Ischemic or haemorrhagic stroke&#xD;
&#xD;
          -  Time since stroke onset: 1 month&#xD;
&#xD;
          -  Dysphagia confirmed by videofluoroscopic study with a score &gt;3 in the 8-point&#xD;
             Penetration Aspiration Scale.&#xD;
&#xD;
          -  Mini-mental State Exploration &gt; 24)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Aphasia&#xD;
&#xD;
          -  History of cardiopulmonary disease; neurologic condition other than stroke and&#xD;
             metabolic disease&#xD;
&#xD;
          -  Medical treatment with potential effect on muscle structure and function&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anna Guillén-Solà, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundació IMIM - Parc de Salut Mar</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital de l'Esperança</name>
      <address>
        <city>Barcelona</city>
        <state>Catalonia</state>
        <zip>08024</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Physical Medicine &amp; Rehabilitation Dpt. Parc de Salut Mar.</name>
      <address>
        <city>Barcelona</city>
        <zip>08024</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke. 2005 Dec;36(12):2756-63. doi: 10.1161/01.STR.0000190056.76543.eb. Epub 2005 Nov 3.</citation>
    <PMID>16269630</PMID>
  </reference>
  <reference>
    <citation>Guillen-Sola A, Messagi Sartor M, Bofill Soler N, Duarte E, Barrera MC, Marco E. Respiratory muscle strength training and neuromuscular electrical stimulation in subacute dysphagic stroke patients: a randomized controlled trial. Clin Rehabil. 2017 Jun;31(6):761-771. doi: 10.1177/0269215516652446. Epub 2016 Jun 7.</citation>
    <PMID>27271373</PMID>
  </reference>
  <reference>
    <citation>Messaggi-Sartor M, Guillen-Sola A, Depolo M, Duarte E, Rodriguez DA, Barrera MC, Barreiro E, Escalada F, Orozco-Levi M, Marco E. Inspiratory and expiratory muscle training in subacute stroke: A randomized clinical trial. Neurology. 2015 Aug 18;85(7):564-72. doi: 10.1212/WNL.0000000000001827. Epub 2015 Jul 15.</citation>
    <PMID>26180145</PMID>
  </reference>
  <reference>
    <citation>Kulnik ST, Birring SS, Moxham J, Rafferty GF, Kalra L. Does respiratory muscle training improve cough flow in acute stroke? Pilot randomized controlled trial. Stroke. 2015 Feb;46(2):447-53. doi: 10.1161/STROKEAHA.114.007110. Epub 2014 Dec 11.</citation>
    <PMID>25503549</PMID>
  </reference>
  <reference>
    <citation>Burgos R, Sarto B, Elio I, Planas M, Forga M, Canton A, Trallero R, Munoz MJ, Perez D, Bonada A, Salo E, Lecha M, Enrich G, Salas-Salvado J; Group for the Study of Malnutrition in Hospitals in Catalonia. Prevalence of malnutrition and its etiological factors in hospitals. Nutr Hosp. 2012 Mar-Apr;27(2):469-76. doi: 10.1590/S0212-16112012000200018.</citation>
    <PMID>22732970</PMID>
  </reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>September 18, 2020</last_update_submitted>
  <last_update_submitted_qc>September 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2020</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>Deglutition Disorders</mesh_term>
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Malnutrition</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/NCT03021252
org study id: PSM/RHB/NR21
nct id: NCT03021252
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Clinical randomized clinical trial to assess the effectiveness of incorporating inspiratory
      and expiratory muscle training (IEMT) in the rehabilitation of stroke patients with dysphagia
      in terms of functional outcomes, comorbidities, survival and quality of life.

      This project also incorporates a longitudinal study to assess the clinical impact of
      dysphagia on body composition and nutritional status in stroke patients.
Stroke is a major cause of morbidity and mortality worldwide. Stroke can lead to varying
      degrees of oropharyngeal dysphagia (25-85% of patients) and respiratory muscle dysfunction
      associated with an increase in medical complications such as bronchoaspiration, malnutrition
      and death. Dysphagia is present in a significant proportion of patients admitted to
      Rehabilitation (up to 85% depending on series) in stroke. Standard swallow therapy consists
      of educational intervention aimed to improve self-management of dysphagia and protect the
      airway, oral exercises to improve lingual praxis, and compensatory techniques based on
      videofluoroscopic findings. Recent studies suggest that IEMT can improve swallowing efficacy
      and reduce eventual bronchoaspiration events.

      Nutritional status appears in 9-67% of patients with acute and subacute stroke and has an
      impact on functional outcomes and provides information about the risk of hospitalization and
      death. Stroke patients are at risk of developing malnutrition because of neurologic
      impairments related to feeding (chewing, deglutition and self-feeding) that can result in a
      poor food intake. To date, there is only few studies on prevalence and influence of
      malnutrition in stroke.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change in respiratory muscle strength
time frame: Baseline and weekly during 8 weeks
description: Respiratory muscle strength is assessed through maximal inspiratory and expiratory pressures (PImax and PEmax, respectively) using a pressure transducer connected to a digital register system. The PImax is measured at mouth during a maximum effort from residual volume against occluded airway. To determine the PEmax, the patients will perform a maximum expiratory effort from total lung capacity (TLC) in the face of the occluded airway. A specific and validated respiratory pressures manometer will be used (Micro RPM, Cardinalhealth, Kent, UK).
measure: Change in dysphagia severity
time frame: Baseline, 8 weeks, 6 months post-stroke
description: Dysphagia severity is assessed with the Penetration-Aspiration Scale: scores of 1-2 indicate normal swallowing; 3-5, penetration; >6, aspiration.
measure: Change in tongue strength
time frame: Baseline and weekly during 8 weeks
description: Lingual Force (IOPI system): maximum isometric tongue pressure defined as the highest of the three peak isometric tongue pressure scores.
measure: Change in fat-free mass
time frame: Baseline, 3 months and 6 months post-stroke
description: Fat-free mass measured by electrical bioimpedance in kilograms and expressed as normal, low or high values according to normal values for the reference population
measure: Malnutrition at 6 months
time frame: Baseline and 6 months post-stroke
description: Malnutrition criteria of the European Society of Clinical Nutrition and Metabolism (ESPEN)
arm group label: High intensity IEMT
arm group type: Experimental
description: Inspiratory and expiratory muscle training + standard swallow therapy.
arm group label: Sham IEMT
arm group type: Sham Comparator
description: Sham inspiratory and expiratory muscle training + standard swallow therapy
intervention type: Device
intervention name: High intensity IEMT
description: Training load will be the maximum inspiratory / expiratory load defined according to patient tolerance equivalent to 10 maximal repetitions (RM) as 10 consecutive inspirations / expirations (x 5 set), three times per day, during 8 weeks. External loads will be increased weekly at intervals of 10 cm H2O as tolerated. Patients will receive standard swallow therapy consisting of swallowing manoeuvres, oral exercises, and compensatory techniques aimed to improve self-management of dysphagia and protect the airway.
arm group label: High intensity IEMT
intervention type: Device
intervention name: Sham IEMT
description: 5 sets of 10 inspirations and expirations in a sham IEMT trainer, three times a day, during 8 weeks.
arm group label: Sham IEMT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Anna Guillén-Solà, MD, PhD
role: Principal Investigator
affiliation: Fundació IMIM - Parc de Salut Mar
facility: 
facility: 
country: Spain
citation: Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke. 2005 Dec;36(12):2756-63. doi: 10.1161/01.STR.0000190056.76543.eb. Epub 2005 Nov 3.
PMID: 16269630
citation: Guillen-Sola A, Messagi Sartor M, Bofill Soler N, Duarte E, Barrera MC, Marco E. Respiratory muscle strength training and neuromuscular electrical stimulation in subacute dysphagic stroke patients: a randomized controlled trial. Clin Rehabil. 2017 Jun;31(6):761-771. doi: 10.1177/0269215516652446. Epub 2016 Jun 7.
PMID: 27271373
citation: Messaggi-Sartor M, Guillen-Sola A, Depolo M, Duarte E, Rodriguez DA, Barrera MC, Barreiro E, Escalada F, Orozco-Levi M, Marco E. Inspiratory and expiratory muscle training in subacute stroke: A randomized clinical trial. Neurology. 2015 Aug 18;85(7):564-72. doi: 10.1212/WNL.0000000000001827. Epub 2015 Jul 15.
PMID: 26180145
citation: Kulnik ST, Birring SS, Moxham J, Rafferty GF, Kalra L. Does respiratory muscle training improve cough flow in acute stroke? Pilot randomized controlled trial. Stroke. 2015 Feb;46(2):447-53. doi: 10.1161/STROKEAHA.114.007110. Epub 2014 Dec 11.
PMID: 25503549
citation: Burgos R, Sarto B, Elio I, Planas M, Forga M, Canton A, Trallero R, Munoz MJ, Perez D, Bonada A, Salo E, Lecha M, Enrich G, Salas-Salvado J; Group for the Study of Malnutrition in Hospitals in Catalonia. Prevalence of malnutrition and its etiological factors in hospitals. Nutr Hosp. 2012 Mar-Apr;27(2):469-76. doi: 10.1590/S0212-16112012000200018.
PMID: 22732970
responsible party type: Sponsor
mesh term: Deglutition Disorders
mesh term: Stroke
mesh term: Malnutrition
sharing ipd: No