<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/NCT04415268</url>
  </required_header>
  <id_info>
    <org_study_id>CIPI/20/119</org_study_id>
    <nct_id>NCT04415268</nct_id>
  </id_info>
  <brief_title>Combined Effect of CFTR Protein Modulator Drugs and Exercise in Cystic Fibrosis</brief_title>
  <official_title>Combined Effect of CFTR Protein Modulator Drugs and Exercise on Pulmonary Function, Fitness, Sweat Test and Quality of Life in Children With Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad Europea de Madrid</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidad Europea de Madrid</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>
      This study aims to assess the effects of programmed exercise combined with CFTR protein&#xD;
      modulator drugs in the cardiorespiratory fitness, strength, functional capacity and agility&#xD;
      in a group of young patients with Cystic Fibrosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The present study is a new clinical trial that extends our previous work intended to assess&#xD;
      the effect of programmed exercise with or without electrical stimulation on cardiorespiratory&#xD;
      fitness, strength, functional capacity and agility in a group of young patients with Cystic&#xD;
      Fibrosis (ECOMIRIN) registered at ClinicalTrials.gov (Identifier: NCT04153669).&#xD;
&#xD;
      After finishing the study, a subset of the participants was treated with either TEZ/IVA or&#xD;
      LUM/IVA per standard of care, as they were considered candidates according to the AEMPS&#xD;
      (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000833-37/ES). Those patients&#xD;
      are expected to complete five months of pharmacological treatment without exercise by June&#xD;
      2020.&#xD;
&#xD;
      Primary Objective To evaluate the effect of an exercise program on physical fitness in cystic&#xD;
      fibrosis patients after 5 months of administration of LUM/IVA or TEZ/IVA in comparison to the&#xD;
      effect produced by the same exercise program before administration of the drug.&#xD;
&#xD;
      Secondary Objectives Other specific objectives include comparing the beneficial effects of&#xD;
      exercise and LUM/IVA or TEZ/IVA on: 1) cardiorespiratory function and muscle strength; 2) the&#xD;
      concentration of chlorine in sweat; and 3) quality of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">June 9, 2020</start_date>
  <completion_date type="Anticipated">May 15, 2021</completion_date>
  <primary_completion_date type="Anticipated">January 29, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single-group non-randomized, prospective. Within-subject multitreatment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Strength</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Changes in strength will be measured using a five repetition maximum test (5RM)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Cardiorespiratory Fitness</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Changes in cardiorespiratory fitness will be measured using a cardiopulmonary exercise test (CPET)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Forced expiratory volume in 1 second (FEV1)</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Changes in FEV1 will be measured using Spirometry (z-score based on Global Lung Function Initiative reference DOI: 10.1016/j.arbres.2017.07.019)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Forced vital capacity (FVC)</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Changes in FVC will be measured using Spirometry (z-score based on Global Lung Function Initiative reference DOI: 10.1016/j.arbres.2017.07.019)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in FEV1/FVC ratio (FEV1%)</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Changes in FEV1/FVC ratio (FEV1%) will be measured using Spirometry (z-score based on Global Lung Function Initiative reference DOI: 10.1016/j.arbres.2017.07.019)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Forced expiratory flow (FEF)</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Changes in FEF will be measured using Spirometry (z-score based on Global Lung Function Initiative reference DOI: 10.1016/j.arbres.2017.07.019)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Physical Activity Questionnaire (PAQ) for children and adolescents</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Changes in physical activity levels will be measured using PAQ-C for children under 14 years of age and PAQ-A for adolescents over 14 years of age.&#xD;
Items 1 to 9 will be used in the physical activity composite score, and means will be calculated to obtain the final PAQ-C activity summary score. Items 1 to 8 will be used in the physical activity composite score, and means will be calculated to obtain the final PAQ-A activity summary score.&#xD;
A score of 1 indicates low physical activity, whereas a score of 5 indicates high physical activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life: Cystic Fibrosis-Questionnaire-Revised (CFQ-R)</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Changes in quality of life will be measures with the Cystic Fibrosis-Questionnaire-Revised (CFQ-R).&#xD;
Scores for each health related quality of life domain are calculated; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sweat chloride level</measure>
    <time_frame>Four assessment points throughout the study: baseline and after each 8-week intervention</time_frame>
    <description>Chloride concentration in sweat (mEq/L) will be measured in the laboratory using an MK II Chloride Analyzer 926S</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">11</enrollment>
  <condition>Cystic Fibrosis in Children</condition>
  <arm_group>
    <arm_group_label>Multitreatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pharmacological treatment per standard of care (whole study length, starting on week 1).&#xD;
Supervised exercise protocol (phase 1, 8 weeks starting on week 9). Unsupervised exercise protocol (phase 2, 8 weeks starting on week 17).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise</intervention_name>
    <description>Surpervised exercise program: Includes a concurrent exercise intervention (strength training and aerobic training), 3 days a week, 60 minutes sessions.</description>
    <arm_group_label>Multitreatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Unsupervised exercise</intervention_name>
    <description>Unsupervised exercise program: The same exercise program learned during the supervised phase will be practiced at home.</description>
    <arm_group_label>Multitreatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CFTR Modulators</intervention_name>
    <description>Standard of care: Lumacaftor with Ivacaftor or Tezacaftor combined with Ivacaftor.&#xD;
For children between 6 and 11 years of age, Lumacaftor 400 mg combined with Ivacaftor 500 mg in total per day, divided into 2 doses per day; for those over 11 years of age, Tezacaftor 100 mg combined with Ivacaftor 150 mg in the morning, adding a dose of Ivacaftor 150 mg at night.&#xD;
https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000833-37/ES</description>
    <arm_group_label>Multitreatment</arm_group_label>
    <other_name>EudraCT Number 2019-000833-37</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  In order to be included, patients must have participated in the ECOMIRIN clinical&#xD;
             trial (ClinicalTrials.gov Identifier: NCT04153669).&#xD;
&#xD;
          -  They must have a previous CF diagnosis, defined as: sweat chlorine ≥ 60 mEq/L and/or&#xD;
             carry two variants of the CFTR gene characterized as pathogenic.&#xD;
&#xD;
          -  Age 6-18 years; eligible to receive treatment with TEZ/IVA or LUM/IVA according to the&#xD;
             AEMPS (LUM/IVA for 6-11 year-old children homozygous for the F508del mutation; TEZ/IVA&#xD;
             for ≥ 12 year-old children homozygous for the Phe508del mutation, as well as&#xD;
             heterozygous for the F508 mutation plus one of the following mutations: P67L, R117C,&#xD;
             L206W, R352Q, A455E, D579G, 711 + 3A G, S945L, S977F, R1070W, D1152H, 2789 + 5G A,&#xD;
             3272-26A G, and 3849 + 10kbC T);&#xD;
&#xD;
          -  Agreement to collaborate in performing static and dynamic pulmonary function tests.&#xD;
&#xD;
          -  Consent of children and/or parents or legal guardians to participate in the study&#xD;
             after having read and understood the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  CF patients not consenting to participate in the study at any time after reading and&#xD;
             understanding the informed consent form will be excluded.&#xD;
&#xD;
          -  CF patients who are not eligible to receive treatment with TEZ/IVA or LUM/IVA&#xD;
             according to the AEMPS during the course of the study will be excluded.&#xD;
&#xD;
          -  Study participants will be excluded if they test positive for any contagious viral&#xD;
             infection that may affect the outcomes (e.g. SARS-CoV-2).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Margarita Perez Ruiz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidad Europea de Madrid</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Margarita Perez Ruiz, MD</last_name>
    <phone>+34912115200</phone>
    <phone_ext>3010</phone_ext>
    <email>margarita.perez@universidadeuropea.es</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Veronica Sanz, MD</last_name>
    <phone>+34915035900</phone>
    <email>veross81@yahoo.es</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Escuela de Doctorado e Investigacion, Universidad Europea</name>
      <address>
        <city>Villaviciosa De Odón</city>
        <zip>28670</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Margarita Perez Ruiz, MD</last_name>
      <phone>+34912115200</phone>
      <phone_ext>3010</phone_ext>
      <email>margarita.perez@universidadeuropea.es</email>
    </contact>
    <contact_backup>
      <last_name>Veronica Sanz, MD</last_name>
      <phone>+34915035900</phone>
      <email>veross81@yahoo.es</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>June 2, 2020</last_update_submitted>
  <last_update_submitted_qc>June 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidad Europea de Madrid</investigator_affiliation>
    <investigator_full_name>Margarita Perez</investigator_full_name>
    <investigator_title>Full Professor in Exercise Physiology, MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Cystic Fibrosis</keyword>
  <keyword>Electrostimulation</keyword>
  <keyword>Combined Training</keyword>
  <keyword>Physical Fitness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <!-- 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/NCT04415268
org study id: CIPI/20/119
nct id: NCT04415268
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to assess the effects of programmed exercise combined with CFTR protein
      modulator drugs in the cardiorespiratory fitness, strength, functional capacity and agility
      in a group of young patients with Cystic Fibrosis.
The present study is a new clinical trial that extends our previous work intended to assess
      the effect of programmed exercise with or without electrical stimulation on cardiorespiratory
      fitness, strength, functional capacity and agility in a group of young patients with Cystic
      Fibrosis (ECOMIRIN) registered at ClinicalTrials.gov (Identifier: NCT04153669).

      After finishing the study, a subset of the participants was treated with either TEZ/IVA or
      LUM/IVA per standard of care, as they were considered candidates according to the AEMPS
      (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000833-37/ES). Those patients
      are expected to complete five months of pharmacological treatment without exercise by June
      2020.

      Primary Objective To evaluate the effect of an exercise program on physical fitness in cystic
      fibrosis patients after 5 months of administration of LUM/IVA or TEZ/IVA in comparison to the
      effect produced by the same exercise program before administration of the drug.

      Secondary Objectives Other specific objectives include comparing the beneficial effects of
      exercise and LUM/IVA or TEZ/IVA on: 1) cardiorespiratory function and muscle strength; 2) the
      concentration of chlorine in sweat; and 3) quality of life.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single-group non-randomized, prospective. Within-subject multitreatment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Strength
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Changes in strength will be measured using a five repetition maximum test (5RM)
measure: Change in Cardiorespiratory Fitness
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Changes in cardiorespiratory fitness will be measured using a cardiopulmonary exercise test (CPET)
measure: Changes in Forced expiratory volume in 1 second (FEV1)
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Changes in FEV1 will be measured using Spirometry (z-score based on Global Lung Function Initiative reference DOI: 10.1016/j.arbres.2017.07.019)
measure: Changes in Forced vital capacity (FVC)
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Changes in FVC will be measured using Spirometry (z-score based on Global Lung Function Initiative reference DOI: 10.1016/j.arbres.2017.07.019)
measure: Changes in FEV1/FVC ratio (FEV1%)
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Changes in FEV1/FVC ratio (FEV1%) will be measured using Spirometry (z-score based on Global Lung Function Initiative reference DOI: 10.1016/j.arbres.2017.07.019)
measure: Changes in Forced expiratory flow (FEF)
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Changes in FEF will be measured using Spirometry (z-score based on Global Lung Function Initiative reference DOI: 10.1016/j.arbres.2017.07.019)
measure: Changes in Physical Activity Questionnaire (PAQ) for children and adolescents
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Changes in physical activity levels will be measured using PAQ-C for children under 14 years of age and PAQ-A for adolescents over 14 years of age.
Items 1 to 9 will be used in the physical activity composite score, and means will be calculated to obtain the final PAQ-C activity summary score. Items 1 to 8 will be used in the physical activity composite score, and means will be calculated to obtain the final PAQ-A activity summary score.
A score of 1 indicates low physical activity, whereas a score of 5 indicates high physical activity.
measure: Change in quality of life: Cystic Fibrosis-Questionnaire-Revised (CFQ-R)
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Changes in quality of life will be measures with the Cystic Fibrosis-Questionnaire-Revised (CFQ-R).
Scores for each health related quality of life domain are calculated; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health.
measure: Sweat chloride level
time frame: Four assessment points throughout the study: baseline and after each 8-week intervention
description: Chloride concentration in sweat (mEq/L) will be measured in the laboratory using an MK II Chloride Analyzer 926S
arm group label: Multitreatment
arm group type: Experimental
description: Pharmacological treatment per standard of care (whole study length, starting on week 1).
Supervised exercise protocol (phase 1, 8 weeks starting on week 9). Unsupervised exercise protocol (phase 2, 8 weeks starting on week 17).
intervention type: Behavioral
intervention name: Exercise
description: Surpervised exercise program: Includes a concurrent exercise intervention (strength training and aerobic training), 3 days a week, 60 minutes sessions.
arm group label: Multitreatment
intervention type: Behavioral
intervention name: Unsupervised exercise
description: Unsupervised exercise program: The same exercise program learned during the supervised phase will be practiced at home.
arm group label: Multitreatment
intervention type: Drug
intervention name: CFTR Modulators
description: Standard of care: Lumacaftor with Ivacaftor or Tezacaftor combined with Ivacaftor.
For children between 6 and 11 years of age, Lumacaftor 400 mg combined with Ivacaftor 500 mg in total per day, divided into 2 doses per day; for those over 11 years of age, Tezacaftor 100 mg combined with Ivacaftor 150 mg in the morning, adding a dose of Ivacaftor 150 mg at night.
https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-000833-37/ES
arm group label: Multitreatment
other name: EudraCT Number 2019-000833-37
criteria: 
gender: All
minimum age: 6 Years
maximum age: 18 Years
healthy volunteers: No
last name: Margarita Perez Ruiz, MD
role: Principal Investigator
affiliation: Universidad Europea de Madrid
last name: Margarita Perez Ruiz, MD
phone: +34912115200
phone ext: 3010
email: margarita.perez@universidadeuropea.es
last name: Veronica Sanz, MD
phone: +34915035900
email: veross81@yahoo.es
facility: 
status: Recruiting
contact: 
contact backup: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Universidad Europea de Madrid
investigator full name: Margarita Perez
investigator title: Full Professor in Exercise Physiology, MD, PhD
mesh term: Cystic Fibrosis
mesh term: Fibrosis