<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/NCT03799354</url>
  </required_header>
  <id_info>
    <org_study_id>ICS Maugeri CE 2241</org_study_id>
    <nct_id>NCT03799354</nct_id>
  </id_info>
  <brief_title>Study on Impact of Maximal Strength Training in Patients With COPD</brief_title>
  <official_title>Study on Impact of Maximal Strength Training in Patients With COPD: Physiological and Clinical Implications</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituti Clinici Scientifici Maugeri SpA</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universita di Verona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Istituti Clinici Scientifici Maugeri SpA</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>
      In the context of pulmonary rehabilitation of COPD patients, recent guidelines and&#xD;
      metanalysis describe that Resistance Training (RT) can be successfully performed alone or in&#xD;
      conjunction with Endurance Training (ET) without evidence of adverse events.&#xD;
&#xD;
      Maximal Strength Training (MST) is a kind of RT typically performed at ~85-90% of 1RM with&#xD;
      maximal velocity to be developed in the concentric phase. Recent literature indicates a&#xD;
      significant amelioration on the Rate of Force Development (RFD) after MST in healthy&#xD;
      subjects, post-menopausal woman and older populations.&#xD;
&#xD;
      When comparing to the conventional ET, MST generates a little change in muscle mass (no&#xD;
      hypertrophy), but a much greater improvement in the RFD. It has been described that neural&#xD;
      adjustments play a major role in the MST-induced adaptations. MST is also well documented to&#xD;
      improve aerobic endurance by improving walking work efficiency.&#xD;
&#xD;
      Only a small cohort study of COPD patients was conducted, describing that MST can&#xD;
      meaningfully improve strength and RFD, with an increase of around 32% for mechanical&#xD;
      efficiency and a decrease of the perceived effort during submaximal job. This improvement&#xD;
      could determine best performances in daily activities and a best quality of life. The main&#xD;
      aims of this physiological pilot randomized controlled trail will be to evaluate feasibility&#xD;
      and efficacy of the MST compared to standard ET on strength, effort tolerance, fatigue,&#xD;
      economy of walking, dyspnea and risk of falls in a populations of COPD patients, in a short&#xD;
      and middle term (6 months).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Exercise intolerance is a cardinal problem existing in patients with Chronic Obstructive&#xD;
      Pulmonary Disease (COPD). Moreover, skeletal muscle dysfunction is a common extra-pulmonary&#xD;
      manifestation, leading to fatigue, decrease in activity of daily living (ADL) performance and&#xD;
      quality of life and increase of risk of falls, mainly in older patients. In the context of&#xD;
      pulmonary rehabilitation, recent guidelines and metanalysis describe that Resistance Training&#xD;
      (RT) can be successfully performed alone or in conjunction with Endurance Training (ET)&#xD;
      without evidence of adverse events.&#xD;
&#xD;
      As concern the RT programs, metanalysis in COPD describe that training have been mainly&#xD;
      performed with the lower limbs and the training intensities are heterogeneous, generally&#xD;
      ranging from 40% to 70% of 1-Repetition Maximum (1-RM).&#xD;
&#xD;
      Maximal Strength Training (MST) is a RT typically performed at ~85-90% of 1RM with maximal&#xD;
      velocity to be developed in the concentric phase. Recent literature indicates a significant&#xD;
      amelioration on the Rate of Force Development (RFD) after MST in healthy subjects,&#xD;
      post-menopausal woman and older populations.&#xD;
&#xD;
      When comparing to the conventional ET, MST generates a little change in muscle mass (no&#xD;
      hypertrophy), but a much greater improvement in the RFD. It has been described that neural&#xD;
      adjustments play a major role in the MST-induced adaptations. MST is also well documented to&#xD;
      improve aerobic endurance by improving walking work efficiency.&#xD;
&#xD;
      Although the mechanisms at the base of MST effect on the mechanical efficiency have not been&#xD;
      completely clarified, there is evidence that changes in the relationships between power and&#xD;
      speed bring to a longer relaxation phase inside the cycle of job, improving the recovery&#xD;
      between contractions.&#xD;
&#xD;
      In this field, only a small cohort study of COPD patients was conducted describing that MST&#xD;
      can meaningfully improve the strength and the RFD, with an increase of around 32% for&#xD;
      mechanical efficiency and a decrease of the perceived effort during submaximal job. This&#xD;
      improvement could determine best performances in daily activities and a best quality of life.&#xD;
      Nevertheless, this study has been conducted only in a small cohort (twelve patients) of&#xD;
      patients with COPD and further studies are necessary to define the impact on the different&#xD;
      components that determine the effort intolerance.&#xD;
&#xD;
      The main aim of this physiological pilot randomized controlled trail will be to test the&#xD;
      feasibility and the efficacy of the MST compared to standard ET on strength, effort&#xD;
      tolerance, fatigue, economy of walking, dyspnea and risk of falls in a populations of COPD&#xD;
      patients, in a short and middle term (6 months).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 18, 2019</start_date>
  <completion_date type="Anticipated">June 15, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 15, 2023</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>
    <intervention_model_description>Pilot randomized controlled trial</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in walking efficiency</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>The text will be executed using a portable metabolimeter detecting oxygen consumption (VO2).&#xD;
After a 10 min of warm up on a treadmill, the patient will walk 5 min at submaximal steady state walking at 4.5 km/h at 5% incline.&#xD;
Using the average of VO2 of the last minute of walking, the walking efficiency will be defined as percentage of change as follows: external work accomplished/ energy expenditure x 100.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Leg Strength by 1-Repetition Maximum on leg press</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>1-Repetition Maximum (1RM) will be evaluated. 1RM will be measured on a horizontal leg press at a knee angle of 90°. 1RM will be recorded as the heaviest lifted load achieved, applying rest periods of ~4 min between test lifts and increments of 5 kg between each trial until failure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in maximal Rate of Force Development (RFD)</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Immediately after the maximal test 1-RM (see above), using the same apparatus, maximal rate of Force Development (RFD) will be assessed using a force platform and applying a load corresponding to 75% of the participant's pre-test 1RM. The subjects will be instructed to execute the lift as rapidly as possible in the concentric phase. RFD will be analyzed as the time difference between 10% and 90% of Peak force.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in maximal effort tolerance</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>It will be evaluated by VO2 consumption on maximal cardiopulmonary exercise test (CPET) on cycloergometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Constant Load Effort tolerance</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>It will be evaluated by evaluated by time of execution of Cardiopulmonary Constant-Load Endurance Test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fatigue (physiological evaluation)</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>To define peripheral and central component of fatigue, before and after CLET, the investigators will test the difference on force produced during a single twitch superimposed on the Maximal Voluntary Contraction (MVC) and the force produced by the electrically evoked Resting Twitch (RT) produced, at rest, 5 seconds after the MVC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fatigue (qualitative evaluation)</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Fatigue Severity Scale (scale measuring fatigue, 9-item scale ranging from 7 = absence of fatigue to 63= maximal presence of fatigue)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Muscle volume</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Sagittal ultrasound images of the Vastus Lateralis (VL) muscle will be recorded with an 8-12 MHz linear transducer. Images will be obtained with a 90° flexion of hip and knee, at 50% of femur length. The pennation angle (hp) of the VL fascicles will be measured as the angle between the VL muscle fascicles and the deep aponeurosis of the insertion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Dyspnea</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Barthel Index Dyspnea (scale measuring dyspnea during basal ADL, 10-item scale ranging from 0 = absence of dyspnea to 100 = maximal dyspnea)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of CRP</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>C reactive protein [CRP] (mg/dl)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Low grade Inflammation</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Evaluation of neutrophils/ lymphocytes ratio</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Tumor necrosis factor alpha</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>TNF-alpha (pg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Interleukin-6</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>IL6 (pg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscular proteolyses by 3-MeH concentration</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Evaluation of urinary 3 Methyl-Histine (3-MeH) (micromol/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Balance (qualitative measure)</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>BERG scale ( scale measuring balance, composed by 14 balance related tasks, ranging from 0 = worse balance to 56= best balance)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>EuroQol 5-D (scale measuring quality of life, composed by 2 sessions: one of 5 questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) with multiple choice ranging from 0 = no problem to 25= very low quality of life and one using Visual Analogic Scale (VAS) to quantify the health status ranging from 0 = worst health condition to 100 = best health condition. The two scale sessions are considered separately.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Satisfaction: Likert Scale</measure>
    <time_frame>at 8 weeks</time_frame>
    <description>Likert Scale 0-4 ( 0=completely unsatisfied, 4= very satisfied).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Falls</measure>
    <time_frame>baseline and 8 months</time_frame>
    <description>Evaluation of the rate of falls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalizations</measure>
    <time_frame>baseline and 8 months</time_frame>
    <description>Evaluation of the rate of hospitalizations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>baseline and 8 months</time_frame>
    <description>Evaluation of deaths (number)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Balance (quantitative measure)</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>The fall risk (FR) assessment will be evaluated by Balance Board.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Maximal strenght training (MST) plus endurance training (ET)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Endurance training (ET)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Maximal strenght training (MST) plus endurance training (ET)</intervention_name>
    <description>Patients will perform an addictive out-patients rehabilitative treatment of 8 weeks (3 times/week, ≥20 training sessions) consisting of:&#xD;
MST- It will consist of four sets of five repetitions on a leg-press with a focus on the rate of force development during the concentric contraction of the quadriceps from a 90° to legs complete extension. The load will be 85-90% of 1RM. When a patient will be able to perform more than five repetitions in a set, the load will be increased. All strength training will be performed on a seated horizontal leg press.&#xD;
ET - A cycling session will follow the MST and last 40 minutes at constant-load, starting from a load intensity corresponding to patient specific AT. The intensity will be gradually increased with a symptom-based progression.</description>
    <arm_group_label>Treatment Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Endurance training (ET)</intervention_name>
    <description>Patients will perform a usual out-patients rehabilitative treatment of 8 weeks (3 times/week, ≥20 training sessions). They will perform ET by cycling sessions that will last 40 minutes/each at constant-load, starting from a load intensity corresponding to patient specific AT, assessed during the baseline incremental test. The intensity will be gradually increased during the sessions with a symptom-based progression, according to the protocol by Maltais and coworkers. A 3-min warm-up and cool-down will be provided. Heart rate (HR), blood pressure, oxygen pulsoxymetry, and symptoms by Borg CR10 scale will be monitored at the beginning and end of each session.&#xD;
Out of the training-days, both groups will continue their normal daily living with modest regular activity, as recommended by their physician.</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COPD clinical definition according to GOLD guidelines with forced expiratory volume&#xD;
             (FEV1)/ forced vital capacity (FVC) &lt; 70%, and FEV1 &lt; 50% of predicted&#xD;
&#xD;
          -  stable clinical condition&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pulmonary diseases other than COPD&#xD;
&#xD;
          -  type II diabetes or other metabolic diseases&#xD;
&#xD;
          -  malign disease&#xD;
&#xD;
          -  a respiratory tract infection within the last 4 wks&#xD;
&#xD;
          -  long oxygen therapy use.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mara Paneroni, MSc, PT</last_name>
    <role>Principal Investigator</role>
    <affiliation>Istituti Clinici Scientifici Maugeri</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mara Paneroni, MSc, PT</last_name>
    <phone>0039+030+8253</phone>
    <phone_ext>122</phone_ext>
    <email>mara.paneroni@icsmaugeri.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Paola Baiardi, Math</last_name>
    <phone>0039+0382+592</phone>
    <phone_ext>599</phone_ext>
    <email>paola.baiardi@icsmaugeri.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>ICS Maugeri IRCCS, Respiratory Rehabilitation of the Institute of Lumezzane</name>
      <address>
        <city>Lumezzane</city>
        <state>Brescia</state>
        <zip>25065</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mara Paneroni, MSc, PT</last_name>
      <phone>0039+030+8253</phone>
      <phone_ext>122</phone_ext>
      <email>mara.paneroni@icsmaugeri.it</email>
    </contact>
    <contact_backup>
      <last_name>Michele Vitacca, MD</last_name>
      <phone>0039+030+8253</phone>
      <phone_ext>182</phone_ext>
      <email>michele.vitacca@icsmaugeri.it</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigare R, Dekhuijzen PN, Franssen F, Gayan-Ramirez G, Gea J, Gosker HR, Gosselink R, Hayot M, Hussain SN, Janssens W, Polkey MI, Roca J, Saey D, Schols AM, Spruit MA, Steiner M, Taivassalo T, Troosters T, Vogiatzis I, Wagner PD; ATS/ERS Ad Hoc Committee on Limb Muscle Dysfunction in COPD. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014 May 1;189(9):e15-62. doi: 10.1164/rccm.201402-0373ST.</citation>
    <PMID>24787074</PMID>
  </reference>
  <reference>
    <citation>Hoff J, Helgerud J, Wisloff U. Maximal strength training improves work economy in trained female cross-country skiers. Med Sci Sports Exerc. 1999 Jun;31(6):870-7. doi: 10.1097/00005768-199906000-00016.</citation>
    <PMID>10378915</PMID>
  </reference>
  <reference>
    <citation>Hoff J, Tjonna AE, Steinshamn S, Hoydal M, Richardson RS, Helgerud J. Maximal strength training of the legs in COPD: a therapy for mechanical inefficiency. Med Sci Sports Exerc. 2007 Feb;39(2):220-6. doi: 10.1249/01.mss.0000246989.48729.39.</citation>
    <PMID>17277584</PMID>
  </reference>
  <reference>
    <citation>Wang E, Helgerud J, Loe H, Indseth K, Kaehler N, Hoff J. Maximal strength training improves walking performance in peripheral arterial disease patients. Scand J Med Sci Sports. 2010 Oct;20(5):764-70. doi: 10.1111/j.1600-0838.2009.01014.x.</citation>
    <PMID>19804581</PMID>
  </reference>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>August 10, 2022</last_update_submitted>
  <last_update_submitted_qc>August 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>rehabilitation</keyword>
  <keyword>resistive training</keyword>
  <keyword>exercise</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</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/NCT03799354
org study id: ICS Maugeri CE 2241
nct id: NCT03799354
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In the context of pulmonary rehabilitation of COPD patients, recent guidelines and
      metanalysis describe that Resistance Training (RT) can be successfully performed alone or in
      conjunction with Endurance Training (ET) without evidence of adverse events.

      Maximal Strength Training (MST) is a kind of RT typically performed at ~85-90% of 1RM with
      maximal velocity to be developed in the concentric phase. Recent literature indicates a
      significant amelioration on the Rate of Force Development (RFD) after MST in healthy
      subjects, post-menopausal woman and older populations.

      When comparing to the conventional ET, MST generates a little change in muscle mass (no
      hypertrophy), but a much greater improvement in the RFD. It has been described that neural
      adjustments play a major role in the MST-induced adaptations. MST is also well documented to
      improve aerobic endurance by improving walking work efficiency.

      Only a small cohort study of COPD patients was conducted, describing that MST can
      meaningfully improve strength and RFD, with an increase of around 32% for mechanical
      efficiency and a decrease of the perceived effort during submaximal job. This improvement
      could determine best performances in daily activities and a best quality of life. The main
      aims of this physiological pilot randomized controlled trail will be to evaluate feasibility
      and efficacy of the MST compared to standard ET on strength, effort tolerance, fatigue,
      economy of walking, dyspnea and risk of falls in a populations of COPD patients, in a short
      and middle term (6 months).
Exercise intolerance is a cardinal problem existing in patients with Chronic Obstructive
      Pulmonary Disease (COPD). Moreover, skeletal muscle dysfunction is a common extra-pulmonary
      manifestation, leading to fatigue, decrease in activity of daily living (ADL) performance and
      quality of life and increase of risk of falls, mainly in older patients. In the context of
      pulmonary rehabilitation, recent guidelines and metanalysis describe that Resistance Training
      (RT) can be successfully performed alone or in conjunction with Endurance Training (ET)
      without evidence of adverse events.

      As concern the RT programs, metanalysis in COPD describe that training have been mainly
      performed with the lower limbs and the training intensities are heterogeneous, generally
      ranging from 40% to 70% of 1-Repetition Maximum (1-RM).

      Maximal Strength Training (MST) is a RT typically performed at ~85-90% of 1RM with maximal
      velocity to be developed in the concentric phase. Recent literature indicates a significant
      amelioration on the Rate of Force Development (RFD) after MST in healthy subjects,
      post-menopausal woman and older populations.

      When comparing to the conventional ET, MST generates a little change in muscle mass (no
      hypertrophy), but a much greater improvement in the RFD. It has been described that neural
      adjustments play a major role in the MST-induced adaptations. MST is also well documented to
      improve aerobic endurance by improving walking work efficiency.

      Although the mechanisms at the base of MST effect on the mechanical efficiency have not been
      completely clarified, there is evidence that changes in the relationships between power and
      speed bring to a longer relaxation phase inside the cycle of job, improving the recovery
      between contractions.

      In this field, only a small cohort study of COPD patients was conducted describing that MST
      can meaningfully improve the strength and the RFD, with an increase of around 32% for
      mechanical efficiency and a decrease of the perceived effort during submaximal job. This
      improvement could determine best performances in daily activities and a best quality of life.
      Nevertheless, this study has been conducted only in a small cohort (twelve patients) of
      patients with COPD and further studies are necessary to define the impact on the different
      components that determine the effort intolerance.

      The main aim of this physiological pilot randomized controlled trail will be to test the
      feasibility and the efficacy of the MST compared to standard ET on strength, effort
      tolerance, fatigue, economy of walking, dyspnea and risk of falls in a populations of COPD
      patients, in a short and middle term (6 months).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Pilot randomized controlled trial
primary purpose: Other
masking: None (Open Label)
measure: Change in walking efficiency
time frame: baseline and 8 weeks
description: The text will be executed using a portable metabolimeter detecting oxygen consumption (VO2).
After a 10 min of warm up on a treadmill, the patient will walk 5 min at submaximal steady state walking at 4.5 km/h at 5% incline.
Using the average of VO2 of the last minute of walking, the walking efficiency will be defined as percentage of change as follows: external work accomplished/ energy expenditure x 100.
measure: Change in Leg Strength by 1-Repetition Maximum on leg press
time frame: baseline and 8 weeks
description: 1-Repetition Maximum (1RM) will be evaluated. 1RM will be measured on a horizontal leg press at a knee angle of 90°. 1RM will be recorded as the heaviest lifted load achieved, applying rest periods of ~4 min between test lifts and increments of 5 kg between each trial until failure.
measure: Change in maximal Rate of Force Development (RFD)
time frame: baseline and 8 weeks
description: Immediately after the maximal test 1-RM (see above), using the same apparatus, maximal rate of Force Development (RFD) will be assessed using a force platform and applying a load corresponding to 75% of the participant's pre-test 1RM. The subjects will be instructed to execute the lift as rapidly as possible in the concentric phase. RFD will be analyzed as the time difference between 10% and 90% of Peak force.
measure: Change in maximal effort tolerance
time frame: baseline and 8 weeks
description: It will be evaluated by VO2 consumption on maximal cardiopulmonary exercise test (CPET) on cycloergometer
measure: Change in Constant Load Effort tolerance
time frame: baseline and 8 weeks
description: It will be evaluated by evaluated by time of execution of Cardiopulmonary Constant-Load Endurance Test
measure: Change in Fatigue (physiological evaluation)
time frame: baseline and 8 weeks
description: To define peripheral and central component of fatigue, before and after CLET, the investigators will test the difference on force produced during a single twitch superimposed on the Maximal Voluntary Contraction (MVC) and the force produced by the electrically evoked Resting Twitch (RT) produced, at rest, 5 seconds after the MVC.
measure: Change in Fatigue (qualitative evaluation)
time frame: baseline and 8 weeks
description: Fatigue Severity Scale (scale measuring fatigue, 9-item scale ranging from 7 = absence of fatigue to 63= maximal presence of fatigue)
measure: Change in Muscle volume
time frame: baseline and 8 weeks
description: Sagittal ultrasound images of the Vastus Lateralis (VL) muscle will be recorded with an 8-12 MHz linear transducer. Images will be obtained with a 90° flexion of hip and knee, at 50% of femur length. The pennation angle (hp) of the VL fascicles will be measured as the angle between the VL muscle fascicles and the deep aponeurosis of the insertion.
measure: Change in Dyspnea
time frame: baseline and 8 weeks
description: Barthel Index Dyspnea (scale measuring dyspnea during basal ADL, 10-item scale ranging from 0 = absence of dyspnea to 100 = maximal dyspnea)
measure: Concentration of CRP
time frame: baseline and 8 weeks
description: C reactive protein [CRP] (mg/dl)
measure: Change in Low grade Inflammation
time frame: baseline and 8 weeks
description: Evaluation of neutrophils/ lymphocytes ratio
measure: Concentration of Tumor necrosis factor alpha
time frame: baseline and 8 weeks
description: TNF-alpha (pg/ml)
measure: Concentration of Interleukin-6
time frame: baseline and 8 weeks
description: IL6 (pg/ml)
measure: Muscular proteolyses by 3-MeH concentration
time frame: baseline and 8 weeks
description: Evaluation of urinary 3 Methyl-Histine (3-MeH) (micromol/ml)
measure: Change in Balance (qualitative measure)
time frame: baseline and 8 weeks
description: BERG scale ( scale measuring balance, composed by 14 balance related tasks, ranging from 0 = worse balance to 56= best balance)
measure: Change in quality of life
time frame: baseline and 8 weeks
description: EuroQol 5-D (scale measuring quality of life, composed by 2 sessions: one of 5 questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) with multiple choice ranging from 0 = no problem to 25= very low quality of life and one using Visual Analogic Scale (VAS) to quantify the health status ranging from 0 = worst health condition to 100 = best health condition. The two scale sessions are considered separately.
measure: Patient Satisfaction: Likert Scale
time frame: at 8 weeks
description: Likert Scale 0-4 ( 0=completely unsatisfied, 4= very satisfied).
measure: Change in Falls
time frame: baseline and 8 months
description: Evaluation of the rate of falls
measure: Hospitalizations
time frame: baseline and 8 months
description: Evaluation of the rate of hospitalizations
measure: Mortality
time frame: baseline and 8 months
description: Evaluation of deaths (number)
measure: Change in Balance (quantitative measure)
time frame: baseline and 8 weeks
description: The fall risk (FR) assessment will be evaluated by Balance Board.
arm group label: Treatment Group
arm group type: Experimental
description: Maximal strenght training (MST) plus endurance training (ET)
arm group label: Control group
arm group type: Active Comparator
description: Endurance training (ET)
intervention type: Other
intervention name: Maximal strenght training (MST) plus endurance training (ET)
description: Patients will perform an addictive out-patients rehabilitative treatment of 8 weeks (3 times/week, ≥20 training sessions) consisting of:
MST- It will consist of four sets of five repetitions on a leg-press with a focus on the rate of force development during the concentric contraction of the quadriceps from a 90° to legs complete extension. The load will be 85-90% of 1RM. When a patient will be able to perform more than five repetitions in a set, the load will be increased. All strength training will be performed on a seated horizontal leg press.
ET - A cycling session will follow the MST and last 40 minutes at constant-load, starting from a load intensity corresponding to patient specific AT. The intensity will be gradually increased with a symptom-based progression.
arm group label: Treatment Group
intervention type: Other
intervention name: Endurance training (ET)
description: Patients will perform a usual out-patients rehabilitative treatment of 8 weeks (3 times/week, ≥20 training sessions). They will perform ET by cycling sessions that will last 40 minutes/each at constant-load, starting from a load intensity corresponding to patient specific AT, assessed during the baseline incremental test. The intensity will be gradually increased during the sessions with a symptom-based progression, according to the protocol by Maltais and coworkers. A 3-min warm-up and cool-down will be provided. Heart rate (HR), blood pressure, oxygen pulsoxymetry, and symptoms by Borg CR10 scale will be monitored at the beginning and end of each session.
Out of the training-days, both groups will continue their normal daily living with modest regular activity, as recommended by their physician.
arm group label: Control group
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Mara Paneroni, MSc, PT
role: Principal Investigator
affiliation: Istituti Clinici Scientifici Maugeri
last name: Mara Paneroni, MSc, PT
phone: 0039+030+8253
phone ext: 122
email: mara.paneroni@icsmaugeri.it
last name: Paola Baiardi, Math
phone: 0039+0382+592
phone ext: 599
email: paola.baiardi@icsmaugeri.it
facility: 
status: Recruiting
contact: 
contact backup: 
country: Italy
citation: Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigare R, Dekhuijzen PN, Franssen F, Gayan-Ramirez G, Gea J, Gosker HR, Gosselink R, Hayot M, Hussain SN, Janssens W, Polkey MI, Roca J, Saey D, Schols AM, Spruit MA, Steiner M, Taivassalo T, Troosters T, Vogiatzis I, Wagner PD; ATS/ERS Ad Hoc Committee on Limb Muscle Dysfunction in COPD. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014 May 1;189(9):e15-62. doi: 10.1164/rccm.201402-0373ST.
PMID: 24787074
citation: Hoff J, Helgerud J, Wisloff U. Maximal strength training improves work economy in trained female cross-country skiers. Med Sci Sports Exerc. 1999 Jun;31(6):870-7. doi: 10.1097/00005768-199906000-00016.
PMID: 10378915
citation: Hoff J, Tjonna AE, Steinshamn S, Hoydal M, Richardson RS, Helgerud J. Maximal strength training of the legs in COPD: a therapy for mechanical inefficiency. Med Sci Sports Exerc. 2007 Feb;39(2):220-6. doi: 10.1249/01.mss.0000246989.48729.39.
PMID: 17277584
citation: Wang E, Helgerud J, Loe H, Indseth K, Kaehler N, Hoff J. Maximal strength training improves walking performance in peripheral arterial disease patients. Scand J Med Sci Sports. 2010 Oct;20(5):764-70. doi: 10.1111/j.1600-0838.2009.01014.x.
PMID: 19804581
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No